Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants.

Pathogenic variants in CDH11 impair cell adhesion and cause Teebi hypertelorism syndrome.

Teebi hypertelorism syndrome (THS; OMIM 145420) is a rare craniofacial disorder characterized by hypertelorism, prominent forehead, short nose with broad or depressed nasal root. Some cases of THS have been attributed to SPECC1L variants. Homozygous variants in CDH11 truncating the transmembrane and intracellular domains have been implicated in Elsahy-Waters syndrome (EWS; OMIM 211380) with hypertelorism.

Inborn Errors of Metabolism: Gyrate Atrophy.

Gyrate atrophy is an autosomal recessive dystrophy in which night blindness starts early in the first decade of life. In the early stages, large areas of retinal pigment epithelium (RPE) and choriocapillaris (CC) atrophy in the far periphery (lobular shape, Fig. 37.

Ciliopathy: Sjögren-Larsson Syndrome.

Glistening yellow-white crystalline inclusions in foveal and parafoveal areas are almost pathognomonic (Fig. 36.1).

Ciliopathy: Alström Syndrome.

Alström syndrome is an autosomal recessive disease with multisystem involvement, including cone-rod dystrophy, hearing loss, type 2 diabetes, insulin resistance with hyperinsulinemia, dilated cardiomyopathy, and progressive hepatic and renal failure. Patients present in childhood with photophobia and nystagmus, and mimic Leber congenital amaurosis (LCA). The fundus shows pigmentary retinopathy with peau d'orange appearance and some fine white dots like drusen around the macula; the disc is pale, with attenuated retinal vessels (Fig.

Ciliopathy: Senior-Løken Syndrome.

Senior-Løken syndrome is a rare autosomal recessive disease with a prevalence of 1:1,000,000. Retinopathy may progress as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or sector RP (Figs. 34.

Ciliopathy: Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6 years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present.

Ciliopathy: Usher Syndrome.

Ciliopathies are a group of disorders caused by a defect in ciliogenesis, ciliary protein trafficking. Because nearly every cell in the body (including the photoreceptors) contains cilia, defects in ciliary proteins typically affect multiple organ systems. Usher syndrome is the most common syndromic cause of retinitis pigmentosa (RP) and accounts for 10-20% of cases of RP Inheritance is autosomal recessive, and the retinal dystrophy is usually rod-cone dystrophy (Figs.

Mitochondrial Disorder: Maternally Inherited Diabetes and Deafness.

Patients with maternally inherited diabetes and deafness (MIDD) have insulin-dependent diabetes with relatively low BMI; usually the onset of the diabetes is during the third or fourth decade of life and it is associated with progressive neurosensory deafness. The fundus shows circumferentially oriented but discontinuous patches of RPE and choriocapillaris (CC) atrophy around the macula, within the arcades (Figs. 31.

Mitochondrial Disorder: Kearns-Sayre Syndrome.

Mitochondrial diseases are multisystem disorders: anemia, myopathy, lactic acidosis, CNS abnormality, endocrine abnormalities, renal disease, sensorineural deafness, and retinal involvement. The clinical abnormalities are heterogeneous, and they usually begin in childhood. Premature death occurs because of cardiac conduction defects.

Psychosocial mediators of dietary change among Hispanic/Latina breast cancer survivors in a culturally tailored dietary intervention.

Objective: To examine psychosocial mediators of the effect of a culturally tailored dietary intervention on dietary change among Hispanic/Latina breast cancer survivors.

Methods: Hispanic/Latina breast cancer survivors (n = 70) were randomized to receive either a 12-week theory-based and culturally tailored dietary change program (intervention group, n = 34), or standard-of-care printed recommendations (control group, n = 36) (ClinicalTrials.gov NCT01414062).

Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The ¡Cocinar Para Su Salud! Randomized Controlled Trial.

Background: Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk.

Methods: Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months.

¡Cocinar Para Su Salud! Development of a Culturally Based Nutrition Education Curriculum for Hispanic Breast Cancer Survivors Using a Theory-Driven Procedural Model.

We developed a theory-based dietary change curriculum for Hispanic breast cancer survivors with the goal of testing the effects of the intervention on change in dietary intake of fruits/vegetables and fat in a randomized, clinical trial. Social cognitive theory and the transtheoretical model were used as theoretical frameworks to structure curriculum components using the Nutrition Education DESIGN Procedure. Formative assessments were conducted to identify facilitators and barriers common to Hispanic women and test the degree of difficulty and appropriateness of program materials.

Barriers to Recruitment and Adherence in a Randomized Controlled Diet and Exercise Weight Loss Intervention Among Minority Breast Cancer Survivors.

Minority recruitment to cancer trials is low and there are limited data on minority adherence to lifestyle modification interventions. We examined factors related to recruitment and adherence to a pilot weight loss intervention among Hispanic and black breast cancer survivors. Participants completed a detailed screening interview to assess barriers to enrollment.

Barriers and facilitators to recruitment to a culturally-based dietary intervention among urban Hispanic breast cancer survivors.

Purpose: The purpose of this study was to understand factors related to recruitment to behavioral intervention trials among Spanish-speaking urban Hispanic breast cancer (BC) survivors.

Methods: Potentially eligible Hispanic BC survivors were recruited from the Columbia University Breast Oncology Clinic, signed informed consent, and completed a screening interview on demographics, medical history, acculturation (Short Acculturation Scale for Hispanics), quality of life (QOL), and perceived benefits/risks of research participation. Trial eligibility criteria included stage 0-III BC, completion of adjuvant treatment, Hispanic, fluency in Spanish, willing to be randomized to active arm (9-session in-person culturally-based ¡Cocinar para su salud! dietary modification program) or control arm (written materials).

Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.

Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model, and preclinical profile of the potent and selective pan PIM kinase inhibitor compound 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor compound 3, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability.

Incision and Curettage Versus Steroid Injection for the Treatment of Chalazia: A Meta-Analysis.

Purpose: To compare the efficacy of the chalazia treatment modalities of incision and curettage (I&C) and intralesional steroid injections (SI).

Methods: Full publications of randomized controlled trials that compared I&C with SI were identified. Aggregated success rate, weighted summary proportions, and weighted pooled relative risk for success were calculated for each method.

Food environments are relevant to recruitment and adherence in dietary modification trials.

Few studies have examined the built environment's role in recruitment to and adherence in dietary intervention trials. Using data from a randomized dietary modification trial of urban Latina breast cancer survivors, we tested the hypotheses that neighborhood produce access could act as a potential barrier and/or facilitator to recruitment, and that a participant's produce availability would be associated with increased fruit/vegetable intake, one of the intervention's targets. Eligible women who lived within a higher produce environment had a non-significant trend towards being more likely to enroll in the trial.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

Background: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors.

Objective: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors.

Design: Participants were randomized to Intervention and Control groups.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

Background: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors.

Objective: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors.

Design: Participants were randomized to Intervention and Control groups.

Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials.

The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.