Objective:To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.Methods:We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS–revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted.Results:Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months.Conclusion:ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study.
The generation of human induced pluripotent stem cells (hiPSCs) represents an exciting advancement with promise for stem cell transplantation therapies as well as for neurological disease modeling. Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. Our results show that human embryonic stem cell-and hiPSC-derived astrocyte progenitors survive longterm after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related astrocyte biology using in vivo disease modeling with significant implications for human neurological diseases currently lacking animal models. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:575-585
Background & Aims
Dietary factors may have a significant role in relapse of disease among patients with ulcerative colitis (UC). However, the relationship between diet and UC is inadequately understood. We analyzed data from the diet’s role in exacerbations of mesalamine maintenance study to determine whether dietary factors affect risk of disease flares in patients with UC.
Methods
We performed a prospective, multi-center, observational study of 412 patients, from 25 sites, with UC in remission during monotherapy with an aminosalicylate. Patients completed a validated food frequency questionnaire at enrollment and were followed for 12 months. We analyzed the relationship between diet and disease remission or flare for groups of macro- and micro-nutrients, as well as food groups previously associated with an increased risk of flare.
Results
Forty-five patients (11%) had a UC relapse within 1 year of study enrollment. When analyzed in tertiles, increasing intake of multiple fatty acids was associated with increasing odds of relapse. In multivariable logistic regression analysis, only myristic acid (Odds Ratio 3.01, 95% CI 1.17 – 7.74) maintained this dose-response relationship. Other foods previously implicated in flares of UC, such as processed meat, alcohol, and foods high in sulfur, were not associated with an increased risk of flare.
Conclusions
In a prospective study of more than 400 patients with UC undergoing treatment with aminosalicylates, we associated high dietary intake of specific fatty acids, including myristic acid (commonly found in palm oil, coconut oil and dairy fats) with an increased risk of flare. These findings can help design interventional studies to evaluate dietary factors in UC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.