Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function (LoF) or gain-of-function (GoF) properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12), and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for LoF and GoF variants. GoF variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age one month), hypertonic, and more often had movement disorders, including hyperekplexia. Patients with LoF variants were older at the time of seizure onset (median age 16 months), hypotonic, and had sleeping disturbances. LoF and GoF variants were disease-causing in both sexes but affected males often carried de novo or hemizygous LoF variants inherited from healthy mothers, whereas all but one affected females had de novo heterozygous GoF variants.

Magnetic resonance imaging in the evaluation of pathologic nipple discharge: indications and imaging findings.

Pathologic nipple discharge (PND) is typically unilateral, spontaneous, involves a single duct, and is serous or bloody in appearance. In patients with PND, breast MRI can be helpful as an additional diagnostic tool when conventional imaging with mammogram and ultrasound are negative. MRI is able to detect the etiology of nipple discharge in 56-61% of cases when initial imaging with mammogram and ultrasound are negative. Advantages to using MRI in evaluation of PND include good visualization of the retroareolar breast and better evaluation of posterior lesions which may not be well evaluated on mammograms and galactograms. It is also less invasive compared to central duct excision. Papillomas and nipple adenomas are benign breast masses that can cause PND and are well visualized on MRI. Ductal ectasia, and infectious etiologies such as mastitis, abscess, and fistulas are additional benign causes of PND that are well evaluated with MRI. MRI is also excellent for evaluation of malignant causes of PND including Paget's disease, ductal carcinoma in-situ and invasive carcinoma. MRI's high negative predictive value of 87-98.2% is helpful in excluding malignant etiologies of PND.

National Survey to Assess Gender, Racial, and Ethnic Differences Among Radiology Residency Applicants Regarding Factors Impacting Program Selection.

RATIONAL AND OBJECTIVES: Radiology has one of the lowest female representation rates in medicine and recruiting female residents is a challenge for some residency programs. There is limited understanding of gender differences among residency applicants during program selection. The study objective is to investigate which program factors were considered most important by radiology residency applicants and to assess for differences by gender, race and ethnicity. MATERIALS AND METHODS: An anonymous survey was distributed electronically to diagnostic and interventional radiology residency programs in the US and Canada via the Association of Program Coordinators in Radiology (APCR). Residents were asked to evaluate the importance of 30 factors during evaluation of residency programs using a 5-point Likert scale (1 = not important, 5 = extremely important). RESULTS: 370 residents and 1 fellow completed the survey. Of the respondents, 269 were male (72.5%) and 101 were female (27.2%). The most important factors to respondents during program selection were program culture (4.42), geographic location (4.17), fellowship placement (4.14), and imaging and/or procedure volume (3.98). There was a significant difference between male and female respondents in the importance of program culture (p = 0.002), composition of current residents (p = 0.007), percentage of current female residents (p < 0.0001), program size (p = 0.047), call schedule (p = 0.025), percentage of female faculty (p < 0.0001), faculty ethnic and racial diversity (p < 0.0001), resident ethnic and racial diversity (p < 0.0001), which female respondents ranked more highly. CONCLUSION: Applicants consider many factors during residency program selection. Program culture, geographic location, fellowship placement and imaging and/or procedural volume were most important. There were significant differences by gender, race and ethnicity in importance of several factors.

Preventing Physician Burnout in Breast Imaging: Scope of the Problem and Keys to Success.

Physicians, including radiologists and specifically breast imagers, face many challenges, and stressors during their daily routine, many of which can contribute to burnout. While there is an increasing body of literature evaluating burnout, including its prevalence in and impact on radiologists, there is a relative lack of information specifically addressing this topic as it relates to breast imaging. This article reviews key concepts in burnout, describes the potential impact on physicians at all levels of training and work, highlights unique aspects to the specialty of breast imaging that may contribute to burnout, and suggests tool and/or strategies that may help to combat and prevent burnout among breast imagers.

Timely Data for Targeted Quality Improvement Interventions: Use of a Visual Analytics Dashboard for Bronchiolitis.

BACKGROUND: Standard methods for obtaining data may delay quality improvement (QI) interventions including for bronchiolitis, a common cause of childhood hospitalization. OBJECTIVE: To describe the use of a dashboard in the context of a multifaceted QI intervention aimed at reducing the use of chest radiographs, bronchodilators, antibiotics, steroids, and viral testing in patients with bronchiolitis. METHODS: This QI initiative took place at Children's Minnesota, a large, not-for-profit children's health care organization. A multidisciplinary bronchiolitis workgroup developed a local clinical guideline and order-set. Delays in obtaining baseline data prompted a pediatric hospitalist and information technology specialist to modify a vendor's dashboard to display data related to bronchiolitis guideline metrics. Patients 2 months to 2 years old with a bronchiolitis emergency department (ED)/inpatient encounter in the period October 1, 2014 to April 30, 2018 were included. The primary outcome was a functioning dashboard; a process measure was the percentage of ED clinician logins. Outcome measures included the percent use of guideline metrics (e.g., bronchodilators) displayed on statistical process control charts (ED vs. inpatient). Balancing measures included length of stay, charge ratios, and hospital revisits. RESULTS: A workgroup (formed October 2015) implemented a bronchiolitis order-set and guideline (February 2016) followed by a bronchiolitis dashboard (August 2016) consolidating disparate data sources loaded within 2 to 4 days of discharge. In total, 35% of ED clinicians logged in. Leaders used the dashboard to target and track interventions such as a bronchodilator order alert. There were improvements in most outcome metrics; however, timing did not suggest direct dashboard impact. ED balancing measures were lower after implementation. CONCLUSION: We described use of a dashboard to support a multifaceted QI initiative for bronchiolitis. Leaders used the dashboard for targeted interventions but the dashboard did not directly impact the observed improvements. Future studies should assess reasons for low individual dashboard use.

Multiregional Utilization of a Mobile Device App for Triage and Transfer of Burn Patients.

Technology and telehealth have the potential to optimize burn care in areas limited by lack of expertise and geographic distance from a Burn Center. This study reports a multicenter, multiregional experience using a mobile phone app to facilitate triage of patients by allowing referring providers to send encrypted photos, thus enhancing the telephone consultation process. A retrospective review was conducted on referrals from August 2016 to July 2017 at three regional Burn Centers that utilize the same mobile phone app. Centers studied are located in the Western, Northeastern, and Southern regions of the United States. Data on numbers of admissions, consults, referral facilities, type of wounds, disposition, and distance from the Burn Centers were recorded. A total of 2011 consults were placed using the mobile phone app from 294 different referring facilities spanning seven states. Utilization of the mobile phone app ranged from 20.4% to 84% among centers. All three centers demonstrated a similar range of consult distances (0-289 miles). Overall, the top three referral diagnoses were scald, contact, and flame burns. Regional differences included a higher percentage of frostbite in the Western region (P < 0.001) and a higher percentage of scald burns in the Northeastern and Southern regions (P < 0.001). The majority of patients at all centers were referred to outpatient clinics for ongoing burn care. Utilization of a mobile phone app appears to be a useful tool in the triage of patients, but further studies are warranted to assess the impact on accuracy of triage, patient outcomes, and reduction of costs.

Rapid selection of Plasmodium falciparum chloroquine resistance transporter gene and multidrug resistance gene-1 haplotypes associated with past chloroquine and present artemether-lumefantrine use in Inhambane District, southern Mozambique.

Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.

[Naturally occurring oseltamivir resistance in influenza A]. / Naturligt forekommende oseltamivirresistens hos influenza A.

During the last two influenza seasons, one of the predominant influenza A types (H1N1) has developed complete resistance to oseltamivir, the primary treatment option. The virus does, however, remain sensitive to zanamavir and amantadine. There is no unequivocal explanation for this slide in the development of resistance. The best prevention strategy remains vaccination of the general population to avoid immunity. Future antiviral treatment calls for knowledge about resistance to existing types of influenza and the availability of all three types of antiviral medication.