Metformin for treatment of cytopenias in children and young adults with Fanconi anemia.

Fanconi anemia (FA), a genetic DNA repair disorder characterized by marrow failure and cancer susceptibility. In FA mice, metformin improves blood counts and delays tumor development. We conducted a single institution study of metformin in nondiabetic patients with FA to determine feasibility and tolerability of metformin treatment and to assess for improvement in blood counts. Fourteen of 15 patients with at least 1 cytopenia (hemoglobin < 10 g/dL; platelet count < 100 000 cells/µL; or an absolute neutrophil count < 1000 cells/µL) were eligible to receive metformin for 6 months. Median patient age was 9.4 years (range 6.0-26.5 ). Thirteen of 14 subjects (93%) tolerated maximal dosing for age; 1 subject had dose reduction for grade 2 gastrointestinal symptoms. No subjects developed hypoglycemia or metabolic acidosis. No subjects had dose interruptions caused by toxicity, and no grade 3 or higher adverse events attributed to metformin were observed. Hematologic response based on modified Myelodysplastic Syndrome International Working Group criteria was observed in 4 of 13 evaluable patients (30.8%; 90% confidence interval, 11.3-57.3). Median time to response was 84.5 days (range 71-128 days). Responses were noted in neutrophils (n = 3), platelets (n = 1), and red blood cells (n = 1). No subjects met criteria for disease progression or relapse during treatment. Correlative studies explored potential mechanisms of metformin activity in FA. Plasma proteomics showed reduction in inflammatory pathways with metformin. Metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefit. This trial was registered at as #NCT03398824.

Using PhotoVoice to Promote Land Conservation and Indigenous Well-Being in Oklahoma.

Indigenous ancestral teachings commonly present individual and community health as dependent upon relationships between human and nonhuman worlds. But how do persons conversant with ancestral teachings effectively convey such perspectives in contemporary contexts, and to what extent does the general tribal citizenry share them? Can media technology provide knowledge keepers with opportunities to communicate their perspectives to larger audiences? What are the implications for tribal citizens' knowledge and views about tribal land use policies? Using a PhotoVoice approach, we collaborated with a formally constituted body of Cherokee elders who supply cultural guidance to the Cherokee Nation government in Oklahoma. We compiled photographs taken by the elders and conducted interviews with them centered on the project themes of land and health. We then developed a still-image documentary highlighting these themes and surveyed 84 Cherokee citizens before and after they viewed it. Results from the pre-survey revealed areas where citizens' perspectives on tribal policy did not converge with the elders' perspectives; however, the post-survey showed statistically significant changes. We conclude that PhotoVoice is an effective method to communicate elders' perspectives, and that tribal citizens' values about tribal land use may change as they encounter these perspectives in such novel formats.

Low-level inorganic arsenic exposure and neuropsychological functioning in American Indian elders.

BACKGROUND: Inorganic arsenic at high and prolonged doses is highly neurotoxic. Few studies have evaluated whether long-term, low-level arsenic exposure is associated with neuropsychological functioning in adults. OBJECTIVES: To investigate the association between long-term, low-level inorganic arsenic exposure and neuropsychological functioning among American Indians aged 64-95. METHODS: We assessed 928 participants in the Strong Heart Study by using data on arsenic species in urine samples collected at baseline (1989-1991) and results of standardized tests of global cognition, executive functioning, verbal learning and memory, fine motor functioning, and speed of mental processing administered during comprehensive follow-up evaluations in 2009-2013. We calculated the difference in neuropsychological functioning for a 10% increase in urinary arsenic with adjustment for sex, age, education, and study site. RESULTS: The sum of inorganic and methylated arsenic species (∑As) in urine was associated with limited fine motor functioning and processing speed. A 10% increase in ∑As was associated with a .10 (95% CI -.20, -.01) decrease on the Finger Tapping Test for the dominant hand and a .13 decrease (95% CI -.21, -.04) for the non-dominant hand. Similarly, a 10% increase in ∑As was associated with a .15 (95% CI -.29, .00) decrease on the Wechsler Adult Intelligence Scale-Fourth Edition Coding Subtest. ∑As was not associated with other neuropsychological functions. CONCLUSIONS: Findings indicate an adverse association between increased urinary arsenic fine motor functioning and processing speed, but not with other neuropsychological functioning, among elderly American Indians.