Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Listeria meningitis and resultant symptomatic hydrocephalus complicating infliximab treatment for ulcerative colitis.

Listeria monocytogenes, an uncommon pathogen, should be considered by clinicians as a source of sepsis and meningitis in the immunocompromised individuals, including those on anti-TNF alpha agents. Immunosuppressant agents including biologic therapies have transformed the management of various rheumatological and dermatological conditions.(1) We report a case of life-threatening L. monocytogenes sepsis and meningitis in a 75-year-old man receiving infliximab for severe ulcerative colitis (UC).

Saccharomycopsis fodiens sp. nov., a rare predacious yeast from three distant localities.

Three strains representing a novel yeast species were recovered as part of independent collections from flower-associated nitidulid beetles in Australia, Costa Rica and the Galapagos Islands, Ecuador. Analysis of the D1/D2 domains of the large subunit rRNA gene indicated that the species belongs to the genus Saccharomycopsis, although the formation of ascospores was not observed. The yeast is capable of necrotrophic parasitism by means of infection pegs when mixed with other yeasts or filamentous fungi. Of particular interest is the fact that despite the large distances separating the isolation sites of the three strains, other strains of the species have not been recovered in other samples of flower-associated nitidulids even though these habitats have been sampled extensively. It is suggested that the dispersal of the yeast may be linked to human historical factors. The name Saccharomycopsis fodiens sp. nov. is proposed for the yeast. The type strain is UWOPS 95-697.4(T) (=CBS 8332(T)=NRRL Y-48786(T)).

Metschnikowia shivogae sp. nov., a yeast species associated with insects of morning glory flowers in East Africa.

The novel species Metschnikowia shivogae is described to accommodate three isolates recovered from insects of morning glory flowers at two localities in East Africa. The isolates differ slightly in rDNA ITS and D1/D2 large-subunit sequences and one isolate featured a two-base heterogeneity that might be the result of recombination between two variant rDNAs. M. shivogae is a sister species to Metschnikowia aberdeeniae and shares the same habitat. The reproductive boundaries of M. aberdeeniae, which were not clear in the past, have now been elucidated further. The type strain of Metschnikowia shivogae sp. nov. is strain SUB 04-310.1(T) (h(+); =CBS 10292(T) =NRRL Y-27924(T)) and the allotype is strain UWOPS 07-203.2 (h(-); =CBS 10770 =NRRL Y-48447).

Metschnikowia orientalis sp. nov., an Australasian yeast from nitidulid beetles.

A novel species, Metschnikowia orientalis sp. nov., is described for haploid, heterothallic yeasts isolated from nitidulid beetles sampled in flowers in Rarotonga in the Cook Islands, and the Cameron Highlands of Malaysia. As evidenced by analysis of D1/D2 large subunit rDNA sequences, the species is related to Candida hawaiiana, to which it is similar in growth responses. Cylindrical, conjugated asci and acicular ascospores of moderate size are formed. Rudimentary mating reactions were observed with Metschnikowia aberdeeniae and Metschnikowia continentalis, but not with C. hawaiiana. The type strain of M. orientalis is UWOPS 99-745.6(T) (h(+)) (=CBS 10331(T)=NRRL Y-27991(T)) and the designated allotype is UWOPS 05-269.1 (h(-)) (=CBS 10330=NRRL Y-27992).

Metschnikowia hamakuensis sp. nov., Metschnikowia kamakouana sp. nov. and Metschnikowia mauinuiana sp. nov., three endemic yeasts from Hawaiian nitidulid beetles.

Three heterothallic, haplontic yeast species, Metschnikowia hamakuensis, Metschnikowia kamakouana and Metschnikowia mauinuiana, are described from isolates associated with endemic nitidulid beetles living on various endemic plants on three Hawaiian islands. As morphospecies, they are similar to Metschnikowia hawaiiensis, but based on mating compatibility and ascospore formation, they can be assigned clearly to distinct biological species. Analysis of ITS/5.8S and D1/D2 large subunit rDNA sequences shows that, with M. hawaiiensis and two other isolates, these species form a distinct subclade within the large-spored Metschnikowia species, indicating that they are Hawaiian endemics. Type cultures are: M. hamakuensis, UWOPS 04-207.1(T) = CBS 10056(T) = NRRL Y-27834(T) (type, h(+)) and UWOPS 04-204.1 = CBS 10055 = NRRL Y-27833 (allotype, h(-)); M. kamakouana, UWOPS 04-112.5(T) = CBS 10058(T) = NRRL Y-27836(T) (type, h(+)) and UWOPS 04-109.1 = CBS 10057 = NRRL Y-27835 (allotype, h(-)); and M. mauinuiana, UWOPS 04-190.1(T) = CBS 10060(T) = NRRL Y-27838(T) (type, h(+)) and UWOPS 04-110.4 = CBS 10059 = NRRL Y-27837 (allotype, h(-)).

Ogataea falcaomoraisii sp. nov., a sporogenous methylotrophic yeast from tree exudates.

Thirteen strains of a new ascospore-forming, methanol-assimilating yeast species were isolated from sap exudates of Sclerolobium sp. (carvoeiro) in two forest fragments in the state of Toncantins, Brazil, and from Hymenaea courbaril (guapinol, jatobá) in Guanacaste Province, Costa Rica. Analysis of the sequences of the D1/D2 large-subunit ribosomal DNA showed that the species belongs to the genus Ogataea (syn. Pichia), and it was described as Ogataea falcaomoraisii. The closest relatives are Candida ortonii and C. nemodendra. The type culture is UFMG-T264-1T (= CBS 9814T = NRRL Y-27756).

Geography and niche occupancy as determinants of yeast biodiversity: the yeast-insect-morning glory ecosystem of Kipuka Puaulu, Hawai'i.

Biodiversity theory proposes two types of hypotheses to account for the species composition of a given community. The first encompasses geographic and historical factors. For example, local species richness is thought to be affected by area, proximity to large landmasses, dispersal mechanisms, and climatic history, collectively known as biogeography. The second type, termed niche occupancy rules, deals with the intrinsic properties of the species as they affect their interaction with the habitat and with other members of the community. The yeast-insect-morning glory ecosystem is a good model to explore biodiversity theory in ascomycetous yeasts. Here we focus on beetles that breed or feed in morning glories and a group of ascomycetous yeasts that are associated exclusively with them. Specifically, we analyse the community found in the vicinity of Kipuka Puaulu, a small patch of disturbed but mature forest situated amidst lava flows on the island of Hawai'i. Major members of the yeast community include Metschnikowia hawaiiensis, Metschnikowia lochheadii, and the related asexual species Candida ipomoeae and Candida kipukae. These species are nearly indistinguishable from one another in terms of nutritional requirements and abilities, although their phylogenetic range is enormous. Their distribution, both global and local, is far from random. As Kipuka Puaulu is an island within an island, the principles of island biogeography may be invoked to explain some aspects of its yeast species composition. M. lochheadii, C. ipomoeae, and the rare species Candida hawaiiana are recent introductions from the American continent and therefore exotic, whereas M. hawaiiensis and C. kipukae might be regarded as endemic, as they are yet to be isolated elsewhere. Vectoring by certain nitidulid beetles explains the long-range dispersal of these species. However, niche occupancy rules may account in part for the local spatial distribution of the yeasts within the island of Hawai'i and within the kipuka itself. We have identified the maximum growth temperature as a potentially critical property of the fundamental niche of these yeasts.

Metschnikowia santaceciliae, Candida hawaiiana, and Candida kipukae, three new yeast species associated with insects of tropical morning glory.

A new haplontic heterothallic species of Metschnikowia and two related asexual yeast species were discovered in morning glory flowers and associated insects. Metschnikowia santaceciliae came from Conotelus (Coleoptera: Nitidulidae) and other insect species associated with flowers of Ipomoea indica (purple morph) in Costa Rica. Candida hawaiiana and Candida kipukae were found in I. indica (syn. I. acuminata) and its insects in Hawai'i, and the former was also isolated in a specimen of Conotelus collected on Merremia tuberosa (Convolvulaceae) in Costa Rica. The three species have nearly identical physiological profiles, typical of the genus Metschnikowia. The sequences of the D1/D2 domains of their large subunit ribosomal DNA confirm that the species belong to the Metschnikowia clade, even though they share a very low degree of inter-relatedness. M. santaceciliae is a sister species to Metschnikowia continentalis. C. kipukae is a basal member of the large-spored Metschnikowia subclade, and C. hawaiiana has a weak affinity to Metschnikowia agaves. Two of the three species appear to be endemic. The type cultures are: Metschnikowia santaceciliae, strains UWO(PS)01-517a1=CBS 9148=NRRL Y-27475 (h(+, holotype) and UWO(PS)01-520a1=CBS 9149=NRRL Y-27476 (h-, isotype); Candida hawaiiana, strain UWO(PS)91-698.3=CBS 9146=NRRL Y-27473; Candida kipukae, strain UWO(PS)00-669.2=CBS 9147=NRRL Y-27474.

Metschnikowia arizonensis and Metschnikowia dekortorum, two new large-spored yeast species associated with floricolous beetles.

Two new haplontic heterothallic species of Metschnikowia were discovered in flowers and associated beetles. Metschnikowia arizonensis was recovered from flowers of cholla cactus (Opuntia echinocarpa) and a specimen of Carpophilus sp. (Coleoptera: Nitidulidae) found in these flowers, in Arizona. Metschnikowia dekortorum was isolated in specimens of the nitidulid beetle Conotelus sp. captured in flowers of two species of Ipomoea in northwestern Guanacaste Province, Costa Rica. The sexual cycle of these yeasts is typical of the large-spored Metschnikowia species, but the asci and spores are intermediate in size between these and other members of the genus. The physiology is consistent with that of most Metschnikowia species except that both species fail to utilize lysine as sole nitrogen source. Also, M. arizonensis utilizes fewer carbon compounds than most species and exhibits considerable variability among strains at this level. Partial ribosomal DNA large-subunit (D1/D2) sequences suggest that M. arizonensis and M. dekortorum are moderately related sister species whose positions are intermediate between the large-spored species Metschnikowia and Metschnikowia hibisci. The type cultures are: M. arizonensis, strains UWO(PS)99-103.3.1=CBS 9064=NRRL Y-27427 (h(+), holotype) and UWO(PS)99-103.4=CBS 9065=NRRL Y-27428 (h(-), isotype); and M. dekortorum, strains UWO(PS)01-142b3=CBS 9063=NRRL Y-27429 (h(+), holotype) and UWO(PS)01-138a3=CBS 9062=NRRL Y-27430 (h(-), isotype).