Resolution of variable expressivity in a multi-generational family using deep clinical phenotyping and models.

Purpose: Variants in result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. haploinsufficiency has been confirmed as the predominant pathway of related neurodevelopmental disorders (NDDs), however, the molecular mechanism underlying the variable clinical presentation remains unclear.

Methods: Here, through work of the Undiagnosed Diseases Network, we identify an undiagnosed individual with an inherited p.

Changes to the ACGME Common Program Requirements and Their Potential Impact on Emergency Medicine Core Faculty Protected Time.

The Accreditation Council for Graduate Medical Education (ACGME), which regulates residency and fellowship training in the United States, recently revised the minimum standards for all training programs. These standards are codified and published as the Common Program Requirements. Recent specific revisions, particularly removing the requirement ensuring protected time for core faculty, are poised to have a substantial impact on emergency medicine training programs.

Limitations of exome sequencing in detecting rare and undiagnosed diseases.

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results.

Whole genome sequencing reveals novel IGHMBP2 variant leading to unique cryptic splice-site and Charcot-Marie-Tooth phenotype with early onset symptoms.

Background: Rare variants (RV) in immunoglobulin mu-binding protein 2 (IGHMBP2) [OMIM 600502] can cause an autosomal recessive type of Charcot-Marie-Tooth (CMT) disease [OMIM 616155], an inherited peripheral neuropathy. Over 40 different genes are associated with CMT, with different possible inheritance patterns.

Methods And Results: An 11-year-old female with motor delays was found to have distal atrophy, weakness, and areflexia without bulbar or sensory findings.

Opportunities for Research in Mental Health Emergencies: Executive Summary and Methodology.

Introduction: Despite the ever-increasing numbers of mental health patients presenting to United States emergency departments, there are large gaps in knowledge about acute care of the behavioral health patient. To address this important problem, the Coalition on Psychiatric Emergencies convened a research consensus conference in December 2016 consisting of clinical researchers, clinicians from emergency medicine, psychiatry and psychology, and representatives from governmental agencies and patient advocacy groups.

Methods: Participants used a standardized methodology to select and rank research questions in the order of importance to both researchers and patients.

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

Rationale: Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families.

Objectives: To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis.

Methods: Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA.

Breast Carcinoma in Childhood and Adolescence: Case Report and Review of the Literature.

Secretory breast carcinoma is a rare tumor originally described in children and adolescent women with a characteristic morphology and a controversial choice of treatment. We report an additional case of a 4-year-old girl with a breast tumor diagnosed as a secretory carcinoma without involvement of the axillary lymph nodes. The therapy consisted of simple mastectomy and low axillary dissection.

A comparison of patient charges associated with percutaneous transluminal coronary angioplasty and coronary artery bypass grafting.

Appropriate interventional treatment for coronary artery disease is an important component in controlling health care expenditures. We conducted a retrospective study to compare the patient charges associated with percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). All patients underwent treatment for left anterior descending coronary artery stenosis over a 3 year 9 month time period from March 1987 to December 1990 and were followed for 7-58 months (median 43 months) after treatment.

Methanol intoxication. Case report.

A 46-year-old male presented to the emergency room seven hours after consuming a large container of sterno. He could not see and complained of abdominal and back pain. He was tachypneic, tachycardic, hypertensive and hypothermic.

Methanol intoxication. How to help patients who have been exposed to toxic solvents.

Methanol intoxication can be a challenge, in part because it is relatively uncommon but also because of the pharmacokinetics involved. A patient may not experience symptoms and thus may not present for treatment for several hours, or even a day or two, after exposure to the toxic substance. Yet, the interval between ingestion and treatment is one of the most important factors in determining patient outcome.

Dietary obesity and weight cycling in rats: a model of stress-induced hypertension?

The present study was designed to reproduce the mild hypertension seen in dietary obese weight-cycled rats [P. Ernsberger and D. O.

Di- and tri-methoxystyryl derivatives of heterocyclic nitrogen compounds.

A series of mono-, di-, and trimethoxystyryl derivatives of heterocyclic nitrogen compounds were prepared to test the N-O-O triangulation hypothesis of Zee-Cheng and Cheng. Of 29 free bases submitted for KB cell culture test, only 2-(3,4-methylenedioxystyryl)benzoxazole and 4-(2,5-dimethoxystyryl)cinnoline were active (ED50 of 4 microgram/ml or less). Methiodide salts were more potent: 8 of 14 were active.

Platinum and palladium derivatives for chemotherapy studies.

Analogues of cis-dichlorodiammineplatinum(II) were prepared in which substituted pyridines (A), 1-(4-aminobenzylidene)indene (B), or DL-3,5,3'5'-tetraoxo-1,2-dipiperazinopropane (ICRF-159) was used in place of ammonia, and in some cases platinum(IV) or palladium(II) was used in place of the platinum(II). Both platinum complexes with ICRF-159 were active against leukemia 1210, but none of the others produced significant life extension following a single ip dose of 400 mg/kg. Attempts to prepare complexes of ICRF-159 with Zn(II), Mn(II), and Cr(III) were unsuccessful, but there were indications of complex formation with CuCl2 and with NiCl2.