Antecedent Disease is Less Prevalent in Amyotrophic Lateral Sclerosis.

BACKGROUND/AIMS: Recent studies suggest that antecedent disease could impact the pathophysiology of the motoneuron disease Amyotrophic Lateral Sclerosis (ALS). We performed a case-control study to examine the prevalence of 11 antecedent diseases in ALS. METHODS: Prevalence of antecedent disease in a 1,288 patient ALS population (Emory University ALS Clinic, Atlanta, Ga., USA) is compared to an age, gender, and geography-matched 7,561 subject control population using a statistical odds ratio (OR) with 95% confidence interval. RESULTS: Association of ALS with odds of arthritis (OR = 0.14); non-ALS neurological disease (OR = 0.14); liver disease (OR = 0.19); chronic obstructive pulmonary disorder or COPD (OR = 0.23); kidney disease (OR = 0.32); adult asthma (OR = 0.39); diabetes (OR = 0.47); hypertension (OR = 0.56); obesity (OR = 0.6); hyperlipidemia or hypercholesterolemia (OR = 0.62); and thyroid disease (OR = 0.78). CONCLUSIONS: The prevalence of antecedent disease was overall less in the ALS population. We present two potential lines of inquiry to explain these results: (1) 'Other disease as ALS protection'--antecedent diseases infer biochemical neuroprotection to ALS; (2) 'ALS as other disease protection'--the underpinnings of ALS could infer protection to other diseases, possibly via the mechanism hypervigilant regulation or 'too-high' regulatory feedback gains.

Undergraduate Biocuration: Developing Tomorrow's Researchers While Mining Today's Data.

Biocuration is a time-intensive process that involves extraction, transcription, and organization of biological or clinical data from disjointed data sets into a user-friendly database. Curated data is subsequently used primarily for text mining or informatics analysis (bioinformatics, neuroinformatics, health informatics, etc.) and secondarily as a researcher resource. Biocuration is traditionally considered a Ph.D. level task, but a massive shortage of curators to consolidate the ever-mounting biomedical "big data" opens the possibility of utilizing biocuration as a means to mine today's data while teaching students skill sets they can utilize in any career. By developing a biocuration assembly line of simplified and compartmentalized tasks, we have enabled biocuration to be effectively performed by a hierarchy of undergraduate students. We summarize the necessary physical resources, process for establishing a data path, biocuration workflow, and undergraduate hierarchy of curation, technical, information technology (IT), quality control and managerial positions. We detail the undergraduate application and training processes and give detailed job descriptions for each position on the assembly line. We present case studies of neuropathology curation performed entirely by undergraduates, namely the construction of experimental databases of Amyotrophic Lateral Sclerosis (ALS) transgenic mouse models and clinical data from ALS patient records. Our results reveal undergraduate biocuration is scalable for a group of 8-50+ with relatively minimal required resources. Moreover, with average accuracy rates greater than 98.8%, undergraduate biocurators are equivalently accurate to their professional counterparts. Initial training to be completely proficient at the entry-level takes about five weeks with a minimal student time commitment of four hours/week.

Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?

Multiple studies have shown that antecedent diseases are less prevalent in amyotrophic lateral sclerosis (ALS) patients than the general age-matched population, which suggests possible neuroprotection. Antecedent disease could be protective against ALS or, conversely, the asymptomatic early physiological underpinnings of ALS could be protective against other antecedent disease. Elucidating the impact of antecedent disease on ALS is critical for assessing diagnostic risk factors, prognostic outcomes, and intervention timing. The objective of this study was to examine the relationship between antecedent conditions and ALS onset age and disease duration (i.e. survival). Medical history surveys for 1439 Emory ALS Clinic patients (Atlanta, GA, USA) were assessed for antecedent hypertension, hyperlipidemia, diabetes, obesity, asthma, arthritis, chronic obstructive pulmonary disease (COPD), thyroid, kidney, liver, and other non-ALS neurological diseases. The ALS onset age and disease duration are compared between the antecedent and non-antecedent populations using chi square, Kaplan-Meier, and ordinal logistic regression. When controlled for confounders, antecedent hypertension (high blood pressure), hyperlipidemia (high cholesterol), arthritis, COPD, thyroid disease, and non-ALS neurological disease are found to be statistically associated with a delayed ALS onset age, whereas antecedent obesity [body mass index (BMI) > 30] was correlated to earlier ALS onset age. With the potential exceptions of liver disease and diabetes (the latter without other common comorbid conditions), antecedent disease is associated with overall shorter ALS disease duration. The unique potential relationship between antecedent liver disease and longer ALS disease duration warrants further investigation, especially given liver disease was found to be a factor of 4-7 times less prevalent in ALS. Notably, most conditions associated with delayed ALS onset are also associated with shorter disease duration. Pathological homeostatic instability exacerbated by hypervigilant regulation (over-zealous homeostatic regulation due to too high regulatory feedback gains) is a viable hypothesis for explaining the early-life protection against antecedent disease and the overall lower antecedent disease prevalence in ALS patients; the later ALS onset age in patients with antecedent disease; and the inverse relationship between ALS onset age and disease duration.