Statistical regularities in natural sounds facilitate the perceptual segregation of auditory sources, or streams. Repetition is one cue that drives stream segregation in humans, but the neural basis of this perceptual phenomenon remains unknown. We demonstrated a similar perceptual ability in animals by training ferrets of both sexes to detect a stream of repeating noise samples (foreground) embedded in a stream of random samples (background). During passive listening, we recorded neural activity in primary auditory cortex (A1) and secondary auditory cortex (posterior ectosylvian gyrus, PEG). We used two context-dependent encoding models to test for evidence of streaming of the repeating stimulus. The first was based on average evoked activity per noise sample and the second on the spectro-temporal receptive field. Both approaches tested whether differences in neural responses to repeating versus random stimuli were better modeled by scaling the response to both streams equally (global gain) or by separately scaling the response to the foreground versus background stream (stream-specific gain). Consistent with previous observations of adaptation, we found an overall reduction in global gain when the stimulus began to repeat. However, when we measured stream-specific changes in gain, responses to the foreground were enhanced relative to the background. This enhancement was stronger in PEG than A1. In A1, enhancement was strongest in units with low sparseness (i.e., broad sensory tuning) and with tuning selective for the repeated sample. Enhancement of responses to the foreground relative to the background provides evidence for stream segregation that emerges in A1 and is refined in PEG.

SIGNIFICANCE STATEMENT To interact with the world successfully, the brain must parse behaviorally important information from a complex sensory environment. Complex mixtures of sounds often arrive at the ears simultaneously or in close succession, yet they are effortlessly segregated into distinct perceptual sources. This process breaks down in hearing-impaired individuals and speech recognition devices. By identifying the underlying neural mechanisms that facilitate perceptual segregation, we can develop strategies for ameliorating hearing loss and improving speech recognition technology in the presence of background noise. Here, we present evidence to support a hierarchical process, present in primary auditory cortex and refined in secondary auditory cortex, in which sound repetition facilitates segregation.

Research suggests that the prevalence of obesity in children with autism spectrum disorder (ASD) is higher than in typically developing children. The US Preventive Services Task Force and the American Academy of Pediatrics (AAP) have endorsed screening children for overweight and obesity as part of the standard of care for physicians. However, the pediatric provider community has been inadequately prepared to address this issue in children with ASD. The Healthy Weight Research Network, a national research network of pediatric obesity and autism experts funded by the US Health Resources and Service Administration Maternal and Child Health Bureau, developed recommendations for managing overweight and obesity in children with ASD, which include adaptations to the AAP’s 2007 guidance. These recommendations were developed from extant scientific evidence in children with ASD, and when evidence was unavailable, consensus was established on the basis of clinical experience. It should be noted that these recommendations do not reflect official AAP policy. Many of the AAP recommendations remain appropriate for primary care practitioners to implement with their patients with ASD; however, the significant challenges experienced by this population in both dietary and physical activity domains, as well as the stress experienced by their families, require adaptations and modifications for both preventive and intervention efforts. These recommendations can assist pediatric providers in providing tailored guidance on weight management to children with ASD and their families.

CONTEXT:

Recommendations conflict regarding universal application of formal screening instruments in primary care (PC) and PC-like settings for autism spectrum disorder (ASD).

Youth suicide is a national and global public health crisis. Pediatricians can use primary and secondary prevention strategies to intervene with youth before or after the onset of suicidal behaviors. Universal suicide risk screening programs can be used to identify youth in medical settings who may otherwise pass through the health care setting with undetected suicide risk. Pediatricians are uniquely positioned to help foster resilience in their young patients and equip families of at-risk youth with safety plans and lethal means safety counseling. Pediatricians on the frontlines of this critical public health crisis require education and training in detecting suicide risk, managing those who screen positive, and connecting their patients to much needed mental health interventions and treatments. Evidence-based suicide risk screening and assessment tools, paired with interventions, are feasible and potentially life-saving in the medical setting.

Nebraska Gov. Pete Ricketts signed a bill into law Wednesday that expands the state's anti-hazing regulations to elementary, middle, and high schools rather than just post-secondary institutions.

While the number of principals running for office has been dwarfed by teachers, school leaders are hoping to change policies in statehouses and in Washington that they say impact their students and families.

Many patient and family demographic characteristics are well-known risk factors for nonurgent emergency-department use. No previous study has examined the primary care physician perspective on parental decisions regarding specific nonurgent emergency-department visits by children.

When discussing specific instances when families in their practices sought nonurgent care for children in the emergency department, physicians believed that parents acted appropriately. Neither parents nor primary care physicians saw nonurgent emergency-department visits as a significant enough problem to warrant change. (Read the full article)

Primary hypertension is a growing concern in adolescents due to its association with the obesity epidemic. Recent studies have examined underdetection and underdiagnosis of hypertension in adolescents but medical management of primary hypertension in adolescents is not well-described.

Our study describes patterns of antihypertensive prescribing for adolescents with primary hypertension including the use of monotherapy versus combination therapy by physicians of different specialties and factors associated with receipt of antihypertensive therapy over a multi-year period. (Read the full article)

Palivizumab administration to well-defined, high-risk groups results in reductions of hospital days, but the intervention is costly. The American Academy of Pediatrics has recommended which groups should be administered palivizumab for the best clinical and cost-effective outcomes.

In a primary practice, palivizumab was frequently used for children outside the recommended groups. Through close oversight and education, the use of palivizumab outside of recommendations was decreased. Palivizumab primary practice usage issues such as proper numbers of doses and timely administration need improvement. (Read the full article)

Recommendations in pediatrics call for general developmental screening of young children; however, research suggests social-emotional development, in particular, is important as an initial indicator of general well-being versus risk, and may warrant inclusion in screening protocols.

Via a social-emotional screening program, significant percentages of children can be identified as being at risk for social-emotional problems, and colocation of an early childhood psychologist promotes the ability to effectively address young children’s social-emotional development within their medical home. (Read the full article)

Clinic-based weight control treatments for youth have largely been designed for preadolescent children and their families by using family-based care, a strategy that may be less appealing to adolescents as they become increasingly motivated by peer acceptance rather than parental influence.

To our knowledge, this is the first study to demonstrate the efficacy of a primary care–based, multicomponent lifestyle intervention specifically tailored for overweight adolescent females and demonstrating a sustained effect (at 12 months) extending beyond the active 5-month intervention. (Read the full article)

There are known gaps in quality measures for children. More clinical effectiveness research is needed. The patient-centered medical home may serve as a model to guide the development of quality measures, particularly for children with complex medical conditions.

This study combined systematic literature review and the Rand/University of California Los Angeles appropriateness method to develop quality measures for children with complex medical conditions. These are valid and feasible quality measures based on the patient-centered medical home framework that may be used to assess care. (Read the full article)

Clinical decision support systems offer a way to help physicians use evidence-based guidelines for screening. Screening patients for common developmental, psychosocial, and behavioral issues informs the clinical decision-making process and may improve patient outcomes.

The Child Health Improvement through Computer Automation system, a clinical decision support system and an electronic medical record, is able to effectively screen patient families in the waiting room by using a tailored questionnaire. The study reveals positive screening rates for identifiable risks in a very large representative urban population by using Child Health Improvement through Computer Automation’s questionnaire. (Read the full article)

Primary care settings provide an important venue for early detection of substance use and intervention, but adolescent screening rates need improvement. Screening and brief interventions appear effective in reducing adult problem drinking but evidence for effectiveness among adolescents is needed.

A computer-facilitated system for screening, feedback, and provider brief advice for primary care can increase adolescent receipt of substance use screening across a variety of practice settings, and shows promise for reducing adolescents’ use of alcohol and cannabis. (Read the full article)

Overweight children are at risk for becoming obese adults, especially if they have an obese parent. Family-based behavioral interventions, largely implemented in specialized settings, have shown efficacy in weight control in youth aged ≥8 years.

This study demonstrates the efficacy of a family-based behavioral weight control program translated to be implemented in the primary care setting. The work underscores the importance of pediatricians intervening early and shifting their focus from the child to the family. (Read the full article)

Filling a prescription is the first step in medication adherence. Unfilled prescriptions are a documented component of nonadherence in adult and pediatric emergency departments and family practices. No one has reported the proportion of unfilled prescriptions in pediatric primary care.

This study identifies the proportion of unfilled prescriptions in a large sample of primary care pediatric patients. It describes clinical and demographic factors associated with prescription filling and suggests that electronic prescribing may improve adherence. (Read the full article)

Practice characteristics, such as practice size, have been associated with the readiness of adult primary care practices for medical home certification. Little is known about how ready primary care practices for children are for medical home certification.

Primary care practices for children attained only 38% of the infrastructure required for medical home certification. Smaller practice size was significantly associated with lower infrastructure scores. Medical home programs need effective approaches to support practices with limited resources. (Read the full article)

Racial disparities in health care have been reported in multiple settings, but not thoroughly examined at the clinician level. The frequent occurrence of respiratory tract infections allows the evaluation of differences in the management of children seen by the same clinician.

Racial differences in the management of common pediatric infections occur among children treated by the same clinician. Given persistent concerns about nonjudicious antibiotic use, examining racial differences may inform our understanding of prescribing practices and identify opportunities for intervention. (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)

Internet, smartphones, and online social media offer new platforms for health promotion and disease management. Few studies have evaluated the use of digital technology among families receiving care in an urban pediatric primary care setting.

Caregivers in an urban pediatric primary care setting have access to and frequently use the Internet, smartphones, and online social media. These technologies may help reach a traditionally hard-to-reach population. (Read the full article)

Pneumococcal conjugate vaccines are effective in preventing pneumococcal disease but are also costly. Although the current US immunization schedule recommends 4 doses, many countries have adopted 3-dose schedules that have worked well, but may provide less protection against pneumococcal disease.

Changing the US 13-valent pneumococcal conjugate vaccine schedule from 3 to 2 primary doses while keeping a booster dose would save $412 million annually but might lead to moderate increases in pneumococcal disease, especially otitis media and pneumonia. (Read the full article)

Because of high costs of newer vaccines, financial risk to private vaccination providers has increased. Previous studies have shown general dissatisfaction with payment for the cost of vaccines and administration fees, with some providers considering no longer providing childhood vaccines.

We show that many providers are dissatisfied with payment for vaccine purchase and administration from all types of payers and that, for new vaccines, providers are using a variety of strategies with parents to handle uncertainty about insurance coverage. (Read the full article)

Primary HHV-7 infection is almost universal by age 5 years and is causally associated with exanthem subitum, febrile seizures, and febrile status epilepticus. The consequences of delayed primary infection are unknown, although encephalitis has been reported in one adult.

Delayed primary HHV-7 infection can cause serious neurologic disease as identified in 3 adolescents, 2 with encephalitis and 1 with Guillain-Barré syndrome. Serologic tests to distinguish primary from past HHV-7 infection are imperative when HHV-7 DNA is present in CSF. (Read the full article)

The Centers for Disease Control and Prevention recommends that health departments in all 50 states deliver AFIX (Assessment, Feedback, Incentives, and eXchange) consultations to 25% of federally funded vaccine providers each year. AFIX effectively raises vaccination coverage among young children.

AFIX consultations achieved short-term gains in coverage for 11- to 12-year-olds for vaccines in the adolescent platform. No gains occurred for older adolescents or over the long term. Consultations were equally effective when delivered in-person or by webinar. (Read the full article)

A substantial gap exists between what is recommended for effective primary care of children and what takes place. Patient-centered health information technologies have been used to gather information and counsel parents, however, have not been integrated directly with electronic health records nor been speech-based to improve decision-making at the point-of-care.

This study shows that a ubiquitous technology, the telephone, can be successfully used to automatically assess and counsel parents before pediatric primary care visits as well as inform their primary care clinicians in a way that is feasible and effective for multiple important issues. (Read the full article)

Overweight and peer victimization are common in childhood and negatively affect health and well-being. Overweight may predispose children to peer victimization, but whether adiposity also increases the risk of bullying perpetration is unclear.

A high BMI at school entry predicts bullying involvement, according to reports of teachers and children themselves. Although trends were visible across the whole BMI spectrum, particularly obese children were victimized and likely to be bully perpetrators. (Read the full article)

Primary ciliary dyskinesia presents in infancy with unexplained neonatal respiratory distress, yet diagnosis is often delayed until late childhood. Earlier diagnosis facilitates earlier onset of therapy, which may help to reduce long-term pulmonary morbidity and mortality.

A diagnostic workup for primary ciliary dyskinesia should be considered in a term infant presenting with unexplained respiratory distress and either lobar collapse, situs inversus, or a prolonged oxygen therapy requirement (>2 days). (Read the full article)

Childhood obesity rates in the United States remain at historic highs. The pediatric primary care office represents an important, underutilized source of intervention. There is a need to test the efficacy of motivational interviewing for pediatric obesity in primary care.

This is among the first large-scale randomized trials to show significant reductions in BMI and that motivational interviewing, delivered by trained providers in the primary care setting, can be an important and feasible part of addressing childhood obesity. (Read the full article)

More than a quarter of child deaths in the United Kingdom are estimated to have identifiable failures in care. Although children account for 40% of the family practice workload, little is known about iatrogenic harm to children in this setting.

This is the first analysis of nationally collected pediatric safety incident reports from family practice. To mitigate harm to children, priority areas requiring improvement include medication provision, referral of unwell children, provision of evidence-based treatment, and adequate diagnosis and assessment. (Read the full article)

More than 200 million children <5 years are not reaching their developmental potential. Lack of stimulating caregiving is a major cause, and effective scalable interventions are needed. Integrating parenting with health services has been recommended, but there are few evaluations.

An innovative parenting intervention can be delivered at routine visits for primary health care, with benefits to child cognitive development and parenting knowledge. This approach using films, discussion, and practice has the potential for delivery at scale. (Read the full article)

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

NEW CASTLE (Jan. 2, 2019) – The number of full-time equivalent primary care physicians providing direct patient care in Delaware in 2018 declined about 6 percent from 2013, a trend that resulted in a slightly lower percentage of physicians statewide who are accepting new patients, according to a new University of Delaware study of the […]

NEW CASTLE (October 9, 2019) – The Department of Health and Social Services (DHSS) is seeking applications from Delaware health care providers for one-time, health information exchange (HIE) support mini-grants to adopt the full range of health information exchange tools offered by the Delaware Health Information Network (DHIN). DHIN is Delaware’s Health Information Exchange (HIE) […]

DEPARTMENT OF INSURANCE: Office of the Commissioner

Sixth SOE modification also protects Delawareans from evictions, foreclosures    WILMINGTON, Del. – Governor John Carney on Tuesday issued a sixth modification to his State of Emergency declaration, moving Delaware’s presidential primary to June 2, and suspending residential foreclosures and evictions during the outbreak of coronavirus (COVID-19). The order goes into effect at 8:00 a.m. on […]

Wilmington. Governor Carney changed the Presidential Primary to June 2, 2020 in his 6th update to the State of Emergency.  The change caused changes in two deadlines. The  deadline to change party affiliation changed April 3, 2020. The  deadline to register to vote changed to May 8, 2020. The Governor also ordered that citizens who […]

All eligible Delaware voters will receive absentee ballot applications by mail WILMINGTON, Del. – Governor John Carney on Thursday signed the fifteenth modification to his State of Emergency declaration, rescheduling Delaware’s presidential primary for July 7. The Delaware Department of Elections will mail absentee ballot applications to all registered Democrats and Republicans in the State of […]

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

In the lead-up to the Truth Matters conference in October, we will be focusing our attention on the sufficiency, authority, and clarity of Scripture. Of our previous blog series, none better embodies that emphasis than Frequently Abused Verses. The following entry from that series originally appeared on October 7, 2015. -ed.

Just as a single cell of cancer can metastasize until it spreads throughout the physical body, a single false doctrine can multiply itself and spread throughout a body of believers. A great forest fire can be started by one spark.^[1] John MacArthur, The MacArthur New Testament Commentary: Galatians (Chicago: Moody Press, 1987), 140.

Throughout this series on Scripture’s “Frequently Abused Verses,” we’ve seen how God’s Word has been misunderstood and misapplied, as well as instances when it is intentionally twisted to accommodate blasphemous lies and spurious doctrines. Today we’re going to consider how the misappropriation of one verse—3 John 2—triggered a heretical movement that has been a scourge for God’s people and blight on the testimony of the church for more than half of a century.

The Roots of the Prosperity Gospel

Not long after Oral Roberts’s death—and amidst a tidal wave of glowing praise for the pioneering televangelist—John MacArthur wrote this summation of the preacher’s life and ministry:

Oral Roberts’s influence is not something Bible-believing Christians should celebrate. Virtually every aberrant idea the Pentecostal and charismatic movements spawned after 1950 can be traced in one way or another to Oral Roberts’s influence.

One of his primary legacies is the prosperity gospel. As John explains in the article quoted above, the prosperity gospel “is the notion that God's favor is expressed mainly through physical health and material prosperity, and that these blessings are available for the claiming by anyone who has sufficient faith.”

Roberts might not have been the first person to teach that false doctrine, but through his television ministry he served as its chief herald and the primary catalyst for its rapid growth and widespread acceptance.

And according to Roberts’s biographer, David Edwin Harrell, Jr., the televangelist’s commitment to the prosperity gospel was born out of a crisis of faith and a new perspective on an overlooked verse.

Out of this period of spiritual trauma came a sequence of instantaneous insights, revelations as Oral viewed them. The first occurred one morning as he read III John 2: “I wish above all things that thou mayest prosper and be in health, even as they soul prospereth.” Oral had rushed out of his house one morning to catch the bus to class when he realized he had not read his Bible as was his custom. He returned, hastily grabbed his Bible, opened it “at random,” and read III John 2. He had read his New Testament, he reported, at least a hundred times, but this verse seemed brand-new. He called Evelyn and read it to her. “That is not in the Bible,” she challenged. “It is,” Oral replied, “I just read it.” “Evelyn,” he said, “we have been wrong. I haven’t been preaching that God is good. And Evelyn, if this verse is right, God is a good God.” The idea seemed revolutionary, liberating. They had been nurtured in a belief system that insisted “you had to be poor to be a Christian.” Perhaps it was not so. They talked excitedly about the verse’s implications. Did it mean they could have a “new car,” a “new house,” a “brand-new ministry?” In later years, Evelyn looked back on that morning as the point of embarkation: “I really believe that that very morning was the beginning of this worldwide ministry that he has had, because it opened up his thinking.”

Oral’s new-found insight was soon put to a practical test. The agent was a Mr. Gustavus, a neighbor who owned the Buick automobile dealership in Enid. Mr. Gus liked Oral, and, although he was a “nonreligious” man, he listened to his neighbor’s preaching occasionally and liked his emphasis on the “here and now.” One morning Mr. Gus noted that Oral’s car looked “pretty bad” and suggested that he buy a new one. It seemed a preposterous idea. Cars were still “practically unobtainable” in these postwar months, and there was no slack in the Robertses’ tight budget. But Mr. Gus showed them a way; he sold their old car for the “highest ceiling” price and acquired a new Buick for Oral at “dealer’s cost.” Mr. Gus, Oral, and Evelyn drove together to Detroit to pick up the car. As they drove back to Enid in their “brand new . . . long, green slick Buick,” Oral and Evelyn pondered the significance of this seemingly impossible turn. Evelyn asked Oral to stop: “We have just got to hold hands and praise the Lord for this car.” For Oral, the “new car became a symbol to me of what a man could do if he would believe God.” Nor was Mr. Gus through. He kept egging Oral on. “Son, the message you are preaching is too big for one town,” he told Oral, “the country is waiting for it. . . . Preach it, son. And you will stir this generation.” ^[2] David Edwin Harrell, Jr., Oral Roberts: An American Life (Bloomington, IN: Indiana University Press, 1985) 65-66.

Of course there are plenty of other Bible verses that have been contorted by prosperity preachers to support their false teaching—we looked at one of them earlier in this series. But 3 John 2 is the textual soil that sprouted Roberts’s prosperity gospel, and the massive family tree of prosperity preachers who have carried on his heretical legacy.

And when you consider how the lies of the prosperity gospel have permeated and poisoned the church, you understand why the details matter, and the damage that can be done when we play fast and loose with God’s Word. The careless reading and application of this one verse has spawned multiple generations of false prophets and fraudulent healers who have feasted on the spiritually naïve and theologically shallow. And by continuing to perpetuate Roberts’s false teaching, they further tarnish the testimony of God’s Word and His people. In many parts of the world, the face of Christianity is a sneering charlatan with his hand out, preaching the get-rich gospel of health and wealth to people who have neither.

When it comes to biblical interpretation, the details are vitally important.

True Prosperity

And in the case of 3 John 2, the details make the true meaning of the verse abundantly clear. In his short letter to a man named Gaius, the apostle John wrote, “Beloved, I pray that in all respects you may prosper and be in good health, just as your soul prospers.”

The reality is that the apostle’s words are not a prophecy of blessing. As John MacArthur explains in his commentary on 3 John, “The phrase ‘I pray that in all respects you may prosper and be in good health’ was a standard greeting in ancient letters.” ^[3] John MacArthur, The MacArthur New Testament Commentary: 1-3 John (Chicago: Moody Press, 2007) 245.

The salutations of the epistles are rich with doctrinal truth (cf. Romans 1:1-7; Galatians 1:1-5; 1 Peter 1:1-2). But it’s not theologically safe or hermeneutically sound to turn a greeting to a specific audience into a promise for all believers.

Moreover, the apostle’s words here don’t support an emphasis on physical blessings like health and wealth, since that’s the opposite of the point John was making. He was praising God for the good report on the quality of Gaius’s character. As John MacArthur explains, the apostle’s focus was spiritual prosperity.

“Prosper” translates a form of the verb euodoō. The term, used only here, Romans 1:10, and 1 Corinthians 16:2, means “to succeed,” “to have things go well,” or “to enjoy favorable circumstances.” The first use of prosper in verse 2 refers to Gaius’s physical health, as the contrast with the last part of the verse makes clear. The apostle’s wish was that Gaius’s physical health would be as good as that of his spiritual.

John’s concern for Gaius is a pastoral desire that he be free from the turmoil, pain, and debilitation of illness so as to be unrestricted in his service to the Lord and His church. . . .

But [in contrast to his physical condition] Gaius’s healthy soul brought far more delight to John. He knew he had a vibrant spiritual life. To borrow from some other apostles, Gaius was among those who are “sound in the faith” (Titus 1:13); constantly “grow[ing] in the grace and knowledge of our Lord and Savior Jesus Christ” (2 Peter 3:18); “walk[ing] in a manner worthy of the Lord, to please him in all respects, bearing fruit in every good work and increasing in the knowledge of God” (Colossians 1:10). ^[4] The MacArthur New Testament Commentary: 1-3 John, 245-246.

When considering how the Lord might bless us, we need to keep in mind that His blessings are not merely for our benefit. As long as He grants us breath, He has use of us for the work of His kingdom. It stands to reason then that even the physical blessings we enjoy have eternal purposes—and for the sake of His glory and His church, we need to pursue those purposes.

God is in the business of building His church, not handing out Buicks.

Title: U.S. Primary Care Docs Unprepared for Surge in Alzheimer's Cases
Category: Health News
Created: 3/11/2020 12:00:00 AM
Last Editorial Review: 3/11/2020 12:00:00 AM

Title: The Doctor Gap: In Areas of Greatest Need, Primary Care Is a Team Effort
Category: Health News
Created: 3/19/2020 12:00:00 AM
Last Editorial Review: 3/20/2020 12:00:00 AM

Despite advances in oral health care, inequalities in oral health outcomes persist due to problems in access. With proper training, primary care providers can mitigate this inequality by providing oral health education, screening, and referral to advanced dental treatment. Diverging sets of oral health competencies and guidelines have been released or endorsed by multiple primary care disciplines. The aim of this study was to transform multiple sets of competencies into Entrustable Professional Activities (EPAs) for oral health integration into primary care training. A scoping review of the literature between January 2000 and December 2016 was conducted according to PRISMA methodology to identify all existing sets of competencies. The following primary care disciplines were included in the search: allopathic/osteopathic medical schools and residency programs in family medicine, internal medicine, and pediatrics; physician assistant programs; and nurse practitioner programs. Competencies were compared using the Health Resources and Services Administration Integration of Oral Health and Primary Care Practice competencies as the foundational set and translated into EPAs. The resulting EPAs were tested with a reactor panel. The scoping review produced 1,466 references, of which 114 were selected for full text review. Fourteen competencies were identified as being central to the integration of oral health into primary care. These were converted to seven EPAs for oral health integration into primary care and were mapped onto Accreditation Council for Graduate Medical Education residency competency domains as well to the Association of American Medical Colleges EPAs for graduating medical students. The resulting EPAs delineate the essential, observable work required of primary care providers to ensure that oral health is treated as a critical determinant of overall health.

ABSTRACT

In the absence of a vaccine, multidrug-resistant Neisseria gonorrhoeae has emerged as a major human health threat, and new approaches to treat gonorrhea are urgently needed. N. gonorrhoeae pili are posttranslationally modified by a glycan that terminates in a galactose. The terminal galactose is critical for initial contact with the human cervical mucosa via an interaction with the I-domain of complement receptor 3 (CR3). We have now identified the I-domain galactose-binding epitope and characterized its galactose-specific lectin activity. Using surface plasmon resonance and cellular infection assays, we found that a peptide mimic of this galactose-binding region competitively inhibited the N. gonorrhoeae-CR3 interaction. A compound library was screened for potential drugs that could similarly prohibit the N. gonorrhoeae-CR3 interaction and be repurposed as novel host-targeted therapeutics for multidrug-resistant gonococcal infections in women. Two drugs, methyldopa and carbamazepine, prevented and cured cervical cell infection by multidrug-resistant gonococci by blocking the gonococcal-CR3 I-domain interaction.

IMPORTANCE Novel therapies that avert the problem of Neisseria gonorrhoeae with acquired antibiotic resistance are urgently needed. Gonococcal infection of the human cervix is initiated by an interaction between a galactose modification made to its surface appendages, pili, and the I-domain region of (host) complement receptor 3 (CR3). By targeting this crucial gonococcal–I-domain interaction, it may be possible to prevent cervical infection in females. To this end, we identified the I-domain galactose-binding epitope of CR3 and characterized its galactose lectin activity. Moreover, we identified two drugs, carbamazepine and methyldopa, as effective host-targeted therapies for gonorrhea treatment. At doses below those currently used for their respective existing indications, both carbamazepine and methyldopa were more effective than ceftriaxone in curing cervical infection ex vivo. This host-targeted approach would not be subject to N. gonorrhoeae drug resistance mechanisms. Thus, our data suggest a long-term solution to the growing problem of multidrug-resistant N. gonorrhoeae infections.

Kaposi sarcoma-associated herpesvirus (KSHV) is necessary but not sufficient for primary effusion lymphoma (PEL) development. Alterations in cellular signaling pathways are also a characteristic of PEL. Other B cell lymphomas have acquired an oncogenic mutation in the myeloid differentiation primary response 88 (MYD88) gene. The MYD88 L265P mutant results in the activation of interleukin-1 receptor associated kinase (IRAK). To probe IRAK/MYD88 signaling in PEL, we employed CRISPR/Cas9 technology to generate stable deletion clones in BCBL-1Cas9 and BC-1Cas9 cells. To look for off-target effects, we determined the complete exome of the BCBL-1Cas9 and BC-1Cas9 cells. Deletion of either MYD88, IRAK4, or IRAK1 abolished interleukin-1 beta (IL-1β) signaling; however, we were able to grow stable subclones from each population. Transcriptome sequencing (RNA-seq) analysis of IRAK4 knockout cell lines (IRAK4 KOs) showed that the IRAK pathway induced cellular signals constitutively, independent of IL-1β stimulation, which was abrogated by deletion of IRAK4. Transient complementation with IRAK1 increased NF-B activity in MYD88 KO, IRAK1 KO, and IRAK4 KO cells even in the absence of IL-1β. IL-10, a hallmark of PEL, was dependent on the IRAK pathway, as IRAK4 KOs showed reduced IL-10 levels. We surmise that, unlike B cell receptor (BCR) signaling, MYD88/IRAK signaling is constitutively active in PEL, but that under cell culture conditions, PEL rapidly became independent of this pathway.

IMPORTANCE One hundred percent of primary effusion lymphoma (PEL) cases are associated with Kaposi sarcoma-associated herpesvirus (KSHV). PEL cell lines, such as BCBL-1, are the workhorse for understanding this human oncovirus and the host pathways that KSHV dysregulates. Understanding their function is important for developing new therapies as well as identifying high-risk patient groups. The myeloid differentiation primary response 88 (MYD88)/interleukin-1 receptor associated kinase (IRAK) pathway, which has progrowth functions in other B cell lymphomas, has not been fully explored in PEL. By performing CRISPR/Cas9 knockout (KO) studies targeting the IRAK pathway in PEL, we were able to determine that established PEL cell lines can circumvent the loss of IRAK1, IRAK4, and MYD88; however, the deletion clones are deficient in interleukin-10 (IL-10) production. Since IL-10 suppresses T cell function, this suggests that the IRAK pathway may serve a function in vivo and during early-stage development of PEL.

The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases.

IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property.

Our study in PNAS (1) applies a mathematically based framework to the study of reported emotional experience evoked by music in the United States and China. Germane to theoretical debate, our methods reveal how specific emotions such as “triumph” are more primary across cultures than valence and arousal, a finding...

Background:

Patient identification is an important step for advance care planning (ACP) discussions.

Purpose:

Clinical evidence shows minimal benefit to vitamin D screening and subsequent treatment in the general population. This study aims to assess the effectiveness of 2 light-touch interventions on reducing vitamin D test orders.

Background

Arteriovenous fistulas placed surgically for dialysis vascular access have a high primary failure rate resulting from excessive inward remodeling, medial fibrosis, and thrombosis. No clinically established pharmacologic or perisurgical therapies currently address this unmet need. Statins’ induction of multiple anti-inflammatory and antithrombotic effects suggests that these drugs might reduce arteriovenous fistula failure. Yet, the in vivo physiologic and molecular effects of statins on fistula patency and maturation remain poorly understood.