BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Background: The horizontal transfer of expressed genes from Bacteria into Ciliates which live in close contact with each other in the rumen (the foregut of ruminants) was studied using ciliate Expressed Sequence Tags (ESTs). More than 4000 ESTs were sequenced from representatives of the two major groups of rumen Cilates: the order Entodiniomorphida (Entodinium simplex, Entodinium caudatum, Eudiplodinium maggii, Metadinium medium, Diploplastron affine, Polyplastron multivesiculatum and Epidinium ecaudatum) and the order Vestibuliferida, previously called Holotricha (Isotricha prostoma, Isotricha intestinalis and Dasytricha ruminantium).

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The importance of the level of dietary fiber intake on bowel function was measured in 16 healthy young males consuming self-selected and liquid enteral diets. Subjects consumed liquid Ensure as their sole nutrient source plus 0 (diet a), 30 (diet c), and 60 (diet d) g/day soy fiber, a fiber source high in hemicellulose that was added to the Ensure. Further, to examine whether heat processing affects the physiologic action of fiber, subjects consumed Enrich, an enteral formula similar to Ensure, which contains 30 g of the same soy fiber (diet b). The four diets were consumed in randomized order each for 10 days. Daily wet stool weight averaged 144.6 g on the self-selected diet and decreased significantly to 67.3 g when Ensure was consumed alone. Average stool weights on diets (b), (c), and (d) were 114.6, 100.2, and 150.3 g/day, respectively. Average fecal dry weights for the four diets were 19.1, 28.7, 25.0, and 30.3 g/day for (a-d), respectively. Gastrointestinal transit time, as measured with radiopaque pellets, was longest on the Ensure diet, 72.4 hr, and approximately 2 days on the fiber-supplemented diets and the self-selected diet. Thus, soy fiber's physiologic effect on laxation was not changed by heat processing. Also, although stool weights were larger on higher fiber intakes, transit rates were similar on all the fiber-containing diets.