Latino populations: a unique opportunity for the study of race, genetics, and social environment in epidemiological research

Latinos are the largest minority population in the United States. Although usually classified as a single ethnic group by researchers, Latinos are heterogeneous from cultural, socioeconomic, and genetic perspectives. From a cultural and social perspective, Latinos represent a wide variety of national origins and ethnic and cultural groups, with a full spectrum of social class. From a genetic perspective, Latinos are descended from indigenous American, European, and African populations. We review the historical events that led to the formation of contemporary Latino populations and use results from recent genetic and clinical studies to illustrate the unique opportunity Latino groups offer for studying the interaction between racial, genetic, and environmental contributions to disease occurrence and drug response.     

Quantitative EEG analysis for assessment to 'plan' a task in amyotrophic lateral sclerosis patients: a study of executive functions (planning) in ALS patients

An attempt has been made to study the ability of patients with amyotrophic lateral sclerosis (ALS) to 'plan' a task. Electroencephalogram (EEG) data corresponding to 'planning of a movement task' is analyzed in comparison with a normal relaxed state. The study was conducted on 12 patients with ALS (6 males, 3 females, mean age 46.75 years) and on same number of controls (10 males, 2 females, mean age 48.75 years) to evaluate a difference in the ability to 'plan' a movement task between them. Patients with ALS were divided in two groups defined by unclear/clear speech. It has been observed that patients with ALS having unclear speech (Group I) showed considerable reduction (p<0.0001) in 'planning' a movement task, whereas patients with ALS having clear speech (Group II) showed no deficit in 'planning' a movement task (p=0.0577), both in comparison with age-matched controls. Apart from supporting the earlier reports of a possible extended neuronal degeneration across wide area of the frontal lobes, the findings reveal a possible reduction in planning, an executive function of the prefrontal cortex of brain, and also reveal that speech impairment may be associated with cognitive deficits in patients with ALS.     

Association of polymorphisms in the collagen region of human SP-A1 and SP-A2 genes with pulmonary tuberculosis in Indian population.

Surfactant protein A (SP-A) binds to and modulates phagocytosis of Mycobacterium tuberculosis by macrophages. We investigated the relationship between polymorphisms in the collagen regions of SP-A1 and SP-A2 genes and pulmonary tuberculosis. In the present study, seven single nucleotide polymorphisms (SNPs) (4 exonic and 3 intronic) have been identified in the collagen regions of SP-A1 and SP-A2 genes in Indian population. Two intronic polymorphisms, SP-A1C1416T ((p = 0.0000, odds ratio (OR) = 20.767,95% CI: 8.315-OR<51.870) and SP-A2C1382G (p = 0.0054; OR = 3.675, 95% CI: 1.400< OR<9.644), showed significant association with pulmonary tuberculosis (number of patients = 10, number of controls = 7). A redundant SNPA1660G of SP-A2gene showed significant association with pulmonary tuberculosis (number of patients = 17, number of controls = 19, p = 0.0000, OR = 8.94,95% CI: 3.311相似文献   

First trimester bleeding evaluation

First trimester bleeding is a common presentation in the emergency room. Ultrasound evaluation of patients with first trimester bleeding is the mainstay of the examination. The important causes of first trimester bleeding include spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease; 50% to 70% of spontaneous abortions are due to genetic abnormalities. In normal pregnancy, the serum beta hCG doubles or increases by at least 66% in 48 hours. The intrauterine GS should be visualized by TVUS with beta hCG levels between 1000 to 2000 mIU/mL IRP. Visualization of the yolk sac within the gestational sac is definitive evidence of intrauterine pregnancy. Embryonic cardiac activity can be identified with CRL of >5 mm. A GS with a mean sac diameter (MSD) of 8 mm or more without a yolk sac and a GS with an MSD of 16 mm or more without an embryo, are important predictors of a nonviable gestation. A GS with a mean sac diameter of 16 mm or more (TVUS) without an embryo is a sonographic sign of anembryonic gestation. A difference of <5 mm between the mean sac diameter and the CRL carries an 80% risk of spontaneous abortion. Approximately 20% of women with first trimester bleeding have a subchorionic hematoma. The presence of an extra ovarian adnexal mass is the most common sonographic finding in ectopic pregnancy. Other findings include the tubal ring sign and hemorrhage. About 26% of ectopic pregnancies have normal pelvic sonograms on TVUS. Complete hydatidiform mole presents with a complex intrauterine mass with multiple anechoic areas of varying sizes (Snowstorm appearance). Twenty-five percent to 65% of molar pregnancies have associated theca-leutin cysts. Arteriovenous malformation of the uterus is a rare but life-threatening cause of vaginal bleeding in the first trimester. The sonographic findings in a patient with first trimester bleeding should be correlated with serum beta hCG levels to arrive at an appropriate clinical diagnosis.     

An innovative medical school curriculum to enhance exposure to genetics and genomics: Updates and outcomes

PurposeIn 2011, we introduced an innovative parallel curriculum at Baylor College of Medicine, formerly called the Genetics Track Curriculum and now called the Genetics and Genomics Pathway, aimed at providing an opportunity for an enriched educational experience throughout medical school. In this report, we describe our 10-year experience with the program and highlight growth in enrollment as well as academic achievements of graduating students.MethodsWe reviewed the data of students enrolled in this pathway, including retention, satisfaction, student-driven curriculum changes, scholarly outcomes, and career outcomes.ResultsFrom September 2011 to June 2021, 121 students were enrolled in the Genetics and Genomics Pathway program. In total, 64 students (64/121 = 53%) left the program before graduating (the majority, after their first year). Of the 57 remaining students, 29 graduated (29/57, approximately 51%), and 4 of the 29 students (4/29 = 14%) matched into a genetics training program.ConclusionThis novel program serves as a mechanism for garnering increased interest and competence in medical genetics. The longitudinal nature of the program fosters enthusiasm for genetics and provides ample opportunity to develop valuable research skills. Given the ongoing shortage of providers in this field, such programs are vital to increase the size of the workforce and broaden the knowledge of providers in diverse fields.     

Characterization of LY2775240, a selective phosphodiesterase‐4 inhibitor,in nonclinical models and in healthy subjects

AbstractLY2775240 is a highly selective, potent and orally‐administered inhibitor of phosphodiesterase 4 (PDE4), and is being investigated as a treatment option for inflammatory disorders, such as psoriasis. LY2775240 was investigated in rodent and rhesus monkey nonclinical models. Treatment with LY2775240 led to significant reductions in TNFα production, a marker of PDE4 engagement upon immune activation, in both nonclinical models. In the first part of a 2‐part first‐in‐human randomized study, a wide dose range of LY2775240 was safely evaluated and found to be well‐tolerated with common adverse events (AEs) of nausea, diarrhea, and headache. No serious AEs were reported. The pharmacokinetic profile of LY2775240 was well‐characterized, with a half‐life that can support once‐a‐day dosing. An ex vivo pharmacodynamic (PD) assay demonstrated dose‐dependent PDE4 target engagement as assessed by reduction in TNFα production. A 20 mg dose of LY2775240 led to near‐maximal TNFα inhibition in this PD assay in the first part of the study and was selected for comparison with the clinical dose of apremilast (30 mg) in the crossover, second part of this study. The 20 mg dose of LY2775240 demonstrated sustained maximal (50%–80%) inhibition of TNFα over all timepoints over the 24‐h duration. The comparator apremilast achieved peak inhibition of ~ 50% at only 4 h postdose with a return to about 10% inhibition within 12 h of dosing. In summary, the nonclinical data and safety, tolerability, and PK/PD data in healthy subjects supports further investigation of LY2775240 in inflammatory indications. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Phosphodiesterase 4 (PDE4) inhibitors, such as apremilast, are currently approved to treat autoimmune disorders, such as psoriasis. LY2775240 is an oral PDE4 inhibitor being developed for treatment of a variety of inflammatory disorders. The degree of enzymatic inhibition achieved by PDE4 inhibitors clinically is poorly understood.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated single ascending doses of LY2775240, a highly selective oral PDE4 inhibitor, in healthy subjects. LY2775240 was well‐tolerated over the dose range evaluated, and pharmacokinetic/pharmacodynamic (PD) profiles were well‐characterized.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study evaluated different doses of LY2775240 and subsequently compared a selected LY2775240 dose with the clinical dose of apremilast with an ex vivo assay. This information builds a connection between target engagement and clinical efficacy.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This is the first report of an ex vivo PD assay that has been systematically implemented in a PDE4 inhibitor Phase 1 study. Early investigation of exposure‐response relationships versus a comparator can support evaluation of clinically meaningful doses of investigational agents.