This study demonstrates a durable beneficial change in the patients' bacterial populations of the colon to represent those of the healthy donor's microbiota. Manipulation of the colonic microbiota to improve its protective and beneficial role represents a promising field of new therapeutic strategies for the treatment of gastrointestinal conditions.

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ObjectiveTo assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis.MethodsUsing peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed.ResultsIn DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses.ConclusionsDMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients.Trial registration numbersEUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770.

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Arc-flank volcaniclastic sedimentation in the Murihiku Terrane of New Zealand lasted about 120 million years from Late Permian to Early Cretaceous time. Despite the effects of pervasive zeolite-facies alteration, whole-rock geochemical parameters for sandstones, siltstones and tuffs record changes in source-rock composition, both in time and along the length of the depositional basin. Sandstones are considered to give a more reliable indication of the state of evolution of the source volcanic arc than do the siltstones. The siltstones commonly contain detrital white mica flakes that are generally lacking in the sandstones, and are possibly of distal continental origin. Some also contain very fine felsic ash particles. Average abundances and normalized multi-element diagrams are used to estimate proportions of three model end-member source constituents, average upper-continental crust (UCC), high-K rhyolite (RHY) and basaltic andesite (AND). Sandstone provenance for the Southland Syncline sector changed from a predominantly basaltic-andesite source in Late Permian to early Middle Triassic time, for example, UCC:RHY:AND = 0:17:83 in the Early to early Middle Triassic, to highly felsic in the Middle to Late Triassic, reaching UCC:RHY:AND = 2:74:24 in the Late Triassic Oretian Stage. A UCC component became increasing significant from latest Triassic upward and the proportion of mafic to felsic volcanism increased again, with UCC:RHY:AND = 15:30:35 in the Middle Jurassic Temaikan Stage. Mix modelling suggests that along-arc source proportions varied, with greater mafic and upper continental crust contributions in the northern Kawhia segment than in the Southland segment. These patterns may be explained by deposition at an oceanic Aleutian-type arc margin, with transition to a continental oceanic arc character induced either by arc evolution and dissection, forearc sliver translation, or underplating of rafted microcontinental fragments.

Background:Fistulizing Crohn's disease (CD) presents a therapeutic challenge as fistulae are notoriously difficult to heal. Mycobacterium avium ss paratuberculosis (MAP) treatment in CD is gaining attention.Aim:We evaluated healing of CD fistula(e) using a novel combination therapy.Study:Nine consecutive patients who failed to heal fistulae on conventional treatment including anti-TNF, were treated with at least three doses of infliximab, 18–30 courses of hyperbaric oxygen therapy and anti-MAP antibiotics comprising rifabutin, clarithromycin and clofazimine.Results:All patients achieved complete healing of fistulae by 6–28 weeks and follow-up for mean 18 months.Conclusion:Combining infliximab, hyperbaric oxygen therapy and anti-MAP, seems to enable healing of recalcitrant fistulae and although a small case series, all nine patients achieved complete healing.

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