AbstractOphioninae is updated, based on the examination of about 800–900 individuals in the South African and European museum collections. A robust interactive matrix key was built to provide quick and reliable identifications. The key is available online at http://www.waspweb.org. Two new species are described: Dicamptusmaxipolsp. n. and Enicospilusgauldetmitchellorumsp. n. Numerous new distribution and biological records are provided, and noticeable morphological intra-specific variations are detailed. Enicospilusbatus Gauld & Mitchell, syn. n. is considered as a junior synonym of Enicospilusluebberti (Enderlein).The revision of the Afrotropical  Ophioninae is one of the two major subfamilies of Ichneumonidae that have been extensively revised in the Afrotropical region. The revision of the Ophioninae is mainly due to The subfamily Ophioninae in the region.It is of note that very few amendments have been brought to their work since the revision was published, except three new species descriptions  and some Natural History Museum, London, UK (Gavin Broad).BMNH California Academy of Science, San Fransisco, USA (Brian Fisher).CASC Muséum d’Histoire Naturelle de La Réunion, Saint Denis, France (Sonia Ribes).MHNR Muséul National d’Histoire Naturelle, Paris, France (Claire Villemant).MNHN Muséum Royal de l’Afrique Centrale, Tervueren, Belgium (Eliane de Coninck).MRAC KwaZulu-Natal Museum, Pietermaritzburg, South Africa (Burgert Muller).NMSA Iziko South African Museum, Cape Town, South Africa (Simon van Noort).SAMChttp://www.waspweb.org.Specimens were point mounted on black, acid-free card for examination (using a Leica M205C stereomicroscope with LED light source), photography and long term preservation. Images were acquired using the Leica LAS 4.4 imaging system, which comprised a Leica® Z16 microscope with a Leica DFC450 Camera with 0.63× video objective attached. The imaging process, using an automated Z-stepper, was managed using the Leica Application Suite V 4.4 software installed on a desktop computer. Lighting was achieved using techniques summarized in PageBreakThe terminology follows : body length, from torulus base to apex of metasoma (mm).B: fore wing length, from tegula base to wing apex (mm).F : shortest distance between eye and mandible / basal mandibular width.ML : distance between outer edges of tentorial pits / median height of clypeus.CT (post-ocellar line index): shortest distance between posterior ocelli / posterior ocellus longest diameter.POL (oculo-ocellar line index): shortest distance between eye and posterior ocellus / posterior ocellus longest diameter.OOL : length of flagellomere 1 (annellus excluded) / length of flagellomere 2.Fl1–2th flagellomere): length / width of flagellomere 20. .Taking into account the taxonomic updates post Gauld and Mitchell’s revision, including the present one, we acknowledge here a total of 194 species of hioninae . A few ihioninae . Finallyhttp://www.waspweb.org.The matrix includes these 194 species and their known intra-specific variability. Furthermore, the dichotomous key provided in Taxon classificationAnimaliaHymenopteraIchneumonidaeRousse & van Noortsp. n.http://zoobank.org/8C1C347B-4AD0-4FB2-A126-242C3FEA947C(verbatim label data). HOLOTYPE ♀: SOUTH AFRICA, W. Cape, West Coast Fossil Park, (5.5 km 270° W Langebaanweg) 32°57.759'S, 18°05.519'E, 9–16 Oct 2002, S. van Noort, Malaise trap LW02-R4-M96, Rehabilitated slimes dam, SAM-HYM-P049469 (SAMC).Orange with inter-ocellar area, most of mesosoma and apex of metasoma black; mandible not twisted, with a central tuft of hairs; clypeus wide, long and flat in profile; antenna short and stout with 56 flagellomeres; mesosoma laterally coarsely punctate to rugose-punctate, dorsally densely and more finely punctate; mesoscutum with notaulus distinct and relatively long; mesopleuron with epicnemial carina not distinct above lower corner of pronotum; propodeum anteriorly densely punctate, posteriorly coarsely rugose-reticulate; disco-submarginal cell with fenestra developed but without distinct sclerite; fore tibia with dense and long spines on outer surface; fore tibial spur with a vestigial basal membrane.Dicamptus species in the world by the absence of distinct sclerites in the disco-submarginal cell; in the Afrotropical region, it seems related to Dicamptusneavei Gauld & Mitchell, 1978, which shares the dense spines on the tibia, the exceptionally reduced ocelli and a somewhat similar colour pattern; Dicamptusneavi is, however, a tropical species with shorter antennae, a stouter metasoma, and distinctly different alar indices with a distinct proximal sclerite in the disco-submarginal cell. In Gauld and Mitchell’s key . B 20.8; F 11.5; ML 1.2; CT 1.2; OOL 2.0; POL 1.2; FI 20%; FColor. Orange interspersed with black; black: inter-ocellar area, entire mesosoma except for mesonotum and metanotum, base of tergite 1, tergite 5 and following, all coxae and trochanters except trochantelli; antenna orange, slightly darkening toward apex; wings hyaline, venation dark reddish to black except for pterostigma anteriorly light reddish.Head. Mandible short and stout, without longitudinal groove, with a central tuft of long hairs, upper tooth barely longer than lower tooth; malar line long; clypeus long and wide, coarsely and densely punctate, rather flat in profile, somewhat swollen medially and ventrally, ventral margin strongly impressed; face strongly transverse, densely and coarsely punctate; frons rather smooth, upper head densely punctate; gena moderately swollen behind eyes; occipital carina complete and strong; antenna short and stout with 56 flagellomeres.PageBreakMesosoma. Pronotum, mesopleuron and metapleuron coarsely and densely punctate, fading to rugose-punctate ventrally; anterior margin of pronotum simple; epicnemial carina short, indistinct above lower corner of pronotum; posterior transverse carina of mesosternum complete though ventrally weak; submetapleural carina not expanded anteriorly; mesoscutum densely and more finely punctate; notaulus long, moderate, distinct to anterior third of mesoscutum; scutellum densely punctate, carinate almost to apex; propodeum with anterior area densely punctate, anterior transverse carina complete, posterior area coarsely rugose-reticulate, abruptly declivous in profile and mid-posteriorly concave. Wings. Disco-submarginal cell with fenestra developed, without any distinct sclerite except a weak quadra centrally; Rs+2r hardly sinuate, slightly bent and thickened near pterostigma; Rs&M distal to cu-a by about its own width; hind wing with 7 hamuli. Legs. Fore tibia with dense and long spines on outer surface; fore tibial spur with a vestigial membrane basally to macrotrichial comb, membrane barely less than 0.1× length of spur; hind coxa in profile 1.8× as long as high; hind trochantellus mid-dorsally 0.2× as long as wide; hind tarsal claws symmetrical with 8 pectinae.Metasoma. Slender; tergite 2 in profile 2.7× longer than high; thyridium large, oval, separated from anterior margin of tergite 2 by 1.3× its own length; ovipositor not reaching beyond metasomal apex.MALE. Unknown.Named after the unusually reduced ocelli, and as a result the large POL. Noun in apposition.South Africa (Western Cape).Taxon classificationAnimaliaHymenopteraIchneumonidaeRousse & van Noortsp. n.http://zoobank.org/5F861712-DBF0-41CC-9854-00DEB2913E86(verbatim label data).HOLOTYPE ♀: Tanzania, Mkomazi Game Reserve, Ibaya Camp, 3.58S 37.48E, 18 April 1996, light trap, S. van Noort, open Combretum bushland, SAM-HYM-P015183 (SAMC).PageBreakYellow orange overall, head paler yellow; mandible with upper tooth distinctly longer than lower tooth; clypeus hardly convex in profile, its ventral margin barely concave and in-turned; occipital carinae complete; gena moderately swollen behind eye; ocelli moderately enlarged; antenna with 56 flagellomeres; pronotum unspecialized; mesopleuron and metapleuron closely and deeply punctate; epicnemial carina laterally indistinct; posterior transverse carina of mesosternum complete and noticeably strong; submetapleural carina slightly broadened anteriorly; notaulus vestigial; propodeum basally punctate, posteriorly coarsely and concentrically striate; fore wing without any sclerite in disco-submarginal cell; fore tibia with dense spines on outer surface; thyridium very shallow.Enicospilus in Afrotropical, Oriental and Australasian regions by the combination of the absence of alar sclerites and the dense spines on fore tibia. The swollen genae and the wing venation make it somewhat related to Enicospilusleucocotis, but this latter is strongly larger, with only sparse spines on tibia and slenderer antenna. In Gauld and Mitchell’s key . B 18.8; F 11.5; ML 0.3; CT 1.6; OOL 0.1; POL 0.4; FI 50%; FColor. Yellowish orange overall with face and orbits paler yellow and apex of metasoma slightly infuscate.Head. Mandible basally constricted, apically parallel-sided and slightly twisted, with upper tooth distinctly longer than lower tooth (greatly worn by abrasion in holotype); outer mandibular surface sparsely setose, without longitudinal groove; labrum 0.3× as long as wide; clypeus in profile hardly convex, its ventral margin barely concave and in-turned; clypeus and face finely and moderately densely punctate; gena moderately swollen behind eye; occipital carina complete; ocelli slightly enlarged; antenna with 56 flagellomeres.PageBreakMesosoma. Pronotum mid-dorsally long, anterior margin simple; mesoscutum densely punctate, notaulus vestigial; scuto-scutellar groove smooth; scutellum densely and shallowly punctate, barely longer than basally wide, carinate to near its apex; mesopleuron and metapleuron closely and deeply punctate, punctures arranged longitudinally but without distinct striation; epicnemial carina short, indistinct above lower corner of pronotum; submetapleural carina weakly broadened anteriorly; posterior transverse carina of mesosternum complete and strong; propodeum with anterior area finely, shallowly and densely punctate, anterior transverse carina complete, posterior area coarsely and concentrically striate Wings. Disco-submarginal cell with fenestra developed, without any distinct sclerite; Rs+2r sinuate; cu-a basal to Rs&M by 0.3× cu-a length; hind wing with 6 hamuli and 1A basally straight. Legs. Fore tibia with numerous dense and long spines on outer surface, basally separated by far less than their own length; hind coxa elongate, in profile 2.4× as long as high; hind trochantellus mid-dorsally 0.2× as long as wide, its apical margin simple; hind tarsal claws symmetrical with 8 pectinae, pectinae long and acute.Metasoma. Slender; tergite 2 in profile 3.2× longer than high; thyridium very shallow, elongate, separated from anterior margin of tergite 2 by 1.7× its own length; ovipositor acute not reaching beyond metasomal apex.PageBreakMALE. Unknown.Enicospilusleucocotis. Let give Gauld what belongs to Gauld (updated after Mark 12:17).This species was probably mentioned in Tanzania.http://isodp.hof-university.de/fuzzyg/query/ and Google Earth http://www.google.com/earth/Provided are the verbatim label data. Only unambiguous identifications are listed. All geographical coordinates are also available on a separate file as Suppl. material Dicamptuspulchellus . The Gambia: 1♀ Kombo Nth district, Bilijo Forest Park, xi.1992, M. Söderlung coll., SAM-HYM-P049471 (SAMC).Euryophionlatipennis . South Africa: 1♀ Kwazulu-Natal, Itala Game Reserve, xii.1992, S. van Noort coll., SAM-HYM-P044187 (SAMC); 1♀ 1♂ same label data except: xii.1999, SAM-HYM-P044163 and SAM-HYM-P044185 (SAMC); Zambia: 1 specimen [apex of metasoma lacking] Southern Province, Choma Nansa farm xii.1993, A.J. Gardiner coll., SAM-HYM-P044072 (SAMC).Laticoleuspalpalis Gauld & Mitchell, 1978. Kenya: 1♀ Eastern Province, Kenplains, x.1984, C.F. Dewhurst coll. (BMNH).Laticoleusunicolor . Botswana: 1♀ Xugana , xi.1979, B.H. Lamoral coll., SAM-HYM-P049474 (SAMC).Lepiscelusdistans . South Africa: 1♀ Kwazulu-Natal, Itala Game Reserve, xii.1999, S. van Noort coll, SAM-HYM-P044186 (SAMC); 1♀ Limpopo, junction Crocodile and Marico Rivers, ii.1918, R. Tucker coll., SAM-HYM-P006194 (SAMC); 2♂♂ Mpumalanga, Nelspruit, i.1939, R.F. Lawrence coll., SAM-HYM-P006193 (SAMC); Zimbabwe: 1♂ Essexvale, ii.1963, SAM-HYM-P006228 (SAMC).Skiapuscoalescens . The Gambia: 1♀ Kombo Nth district, Bilijo Forest Park, xi.1992, M. Söderlung coll., SAM-HYM-P049477 (SAMC).Enicospilusalbiger . Zambia: 1♂ South Luangwa near. Mfuwe, xii.2011, A. Gumovsky coll., SAM-HYM-P049484 (SAMC).Enicospilusbabaulti . Malawi: 1♀ Nyika National Park, Juniper forest, ix.1999, R.J. Murphy coll., SAM-HYM-P021341 (SAMC); South Africa: 1 specimen [metasoma lacking] ii.1917, C.J. Swierstra coll., SAM-HYM-P001398 (SAMC); Zimbabwe: 1♀ Chirinda forest, xi.1955, SAM-HYM-P006247 (SAMC).Enicospilusbebelus Gauld & Mitchell, 1978. Gabon: 1♀ Province Ogoové–Maritime, Réserve des Monts Doudou, iii.2000, S. van Noort coll., SAM-HYM-P041707 (SAMC).PageBreakEnicospilusbetanimenus . Ethiopia: 2♀♀ Adola, xi.1941, SAM-HYM-P047374 and SAM-HYM-P006253 (SAMC); Zimbabwe: 2♀♀ Bulawayo ii.1971, D.K.B. Wheeler coll, SAM-HYM-P006286 (SAMC).Enicospilusbicoloratus Cameron, 1912. Zimbabwe: 1♀ Matopos, ii.1963, SAM-HYM-P006265 (SAMC).Enicospiluscamerunensis . Mayotte: 1♀ Dembéni, iii.2013, G. Cazenove coll. (MHNR).Enicospilusdivisus . Uganda: 1♂ Kibale National Park, Kanyawara, viii.2008, S.van Noort coll., SAM-HYM-P049506 (SAMC).Enicospilusdrakensbergi Gauld & Mitchell, 1978. Tanzania: 1♂ South Pare Mountains, alt. c. 1700m, xi.1995, S. van Noort coll., SAM-HYM-P014698 (SAMC).Enicospilusequatus Gauld & Mitchell, 1978. Central African Republic: 2♀♀ 1♂ Préfecture Sangha-Mbaéré, Réserve Spéciale de Forêt Dense de Dzanga-Sangha, v.2001, S. van Noort coll., SAM-HYM-P049510–P049512 (SAMC).Enicospilusfinalis Gauld & Mitchell, 1978. Central African Republic: 5♀♀ Préfecture Sangha-Mbaéré, Parc National de Dzanga-Ndoki, v.2001, S. van Noort coll., SAM-HYM-P049514 –P049517 (SAMC); Mozambique: 1 specimen [apex of metasoma broken] Mt Gorongoza, ix.1957, SAM-HYM-P006229 (SAMC).Enicospilusoculator Seyrig, 1935. Zimbabwe 1♀ Tuli, v.1959, SAM-HYM-P006232 (SAMC).Enicospilushova Gauld & Mitchell, 1978. Uganda: 1♂ Kibale National Park, Kanyawara, viii.2008, S.van Noort coll., SAM-HYM-P049513 (SAMC).Enicospilusluebberti . 4♀♀ Botswana: 1♀ Xugana , xi.1979, B.H. Lamoral coll. (NMSA).Enicospilusmamatsus Gauld & Mitchell, 1978. South Africa: 1♀ Northern Cape, Sterboom farm, 1599 m, v–vii 2010, S. van Noort, SAM-HYM-P054077 (SAMC).Enicospilusmnous Gauld & Mitchell, 1978. Tanzania: 3♀♀, Mkomazi Game Reserve, xi.1995, H.G. Robertson coll. and S. van Noort colls, SAM-HYM-P014159, SAM-HYM-P014161 and SAM-HYM-P014170 (SAMC); 2♀♀ same label data except: iv.1996, S. van Noort coll., SAM-HYM-P014156 and SAM-HYM-P014706 (SAMC).Enicospilusnesius Gauld & Mitchell, 1978. Central African Republic: 1♀ Préfecture Sangha-Mbaéré, Parc National de Dzanga-Ndoki, v.2001, S. van Noort coll., SAM-HYM-P054079 (SAMC).Enicospiluspallidus . Tanzania: 8♀♀, Mkomazi Game Reserve, xi–xii.1995 and iv.1996, S. van Noort coll., SAM-HYM-P014157–P0141578, SAM-HYM-P014171–P014175 and SAM-HYM-P015200 (SAMC).Enicospiluspolemus Gauld, 1982. South Africa: 1♀ Kwazulu-Natal, Itala Game Reserve, xii.1999, S. van Noort coll., SAM-HYM-P044207 (SAMC); Tanzania: 1♀ Mkomazi Game Reserve, iv–v.1996, S. van Noort coll., SAM-HYM-P015666 (SAMC).PageBreakEnicospilusquietus . Namibia: 1♀ Namib-Naukluft Park, x.1997, S. van Noort coll., SAM-HYM-P020721 (SAMC); 1♂ Otavi, xii.1918, R.M. Lightfoot coll., SAM-HYM-P006278 (SAMC); 1♀ Ondangua Ovamboland, 1921, K.H. Bernard coll., SAM-HYM-P006199 (SAMC); 2 specimens [metasomas lacking] Otjiperongo, i.1931, J.S. Brown coll., SAM-HYM-P047375 (SAMC).Enicospilusrubens . Madagascar: 1♀ Majunga Province, Maintirano District, iii.2008, M.Irwin and R.Harin’Hala colls, MG-44-26 (CASC).Enicospilusrundiensis Bischoff, 1915. Namibia: 1♀ 1♂ Kaross, 1925, SAM-HYM-P001381 (SAMC); 1♀ Warmbad, 1925, SAM-HYM-P001382 (SAMC); 1 specimen [apex of metasoma broken] Narubis, 1921, K.H. Barnard coll., SAM-HYM-P006277 (SAMC); 1 specimen [metasoma lacking] Otjiperongo, i.1931 J.S. Brown coll., SAM-HYM-P006276 (SAMC); Zimbabwe: 1♀ Harare, vi.1961, SAM-HYM-P006225 (SAMC).Enicospilusruscus Gauld & Mitchell, 1978. Kenya: 1♂ Nguruman, vii.2008, S. van Noort coll., SAM-HYM-P054106 (SAMC).Enicospilusbetanimenus . 2♀♀ from Zimbabwe SAM-HYM-P006286 (SAMC) ex Achaeacatella Guenée, 1852 (Lepidoptera: Noctuidae).Enicospilusdubius . 2♀♀ from South Africa (SAMC SAM-HYM-P001508) ex Ctenoplusialimbirina (Guenée) (Lepidoptera: Noctuidae).Enicospilusdolosus . 1♀ from Reunion  ex Anomisflava (Fabricius) (Lepidoptera: Noctuidae).Enicospilusleucocotis . 2♀♀ from South Africa (SAMC SAM-HYM-P046967 and SAM-HYM-P046968) ex Mesocelismontana (Hübner) (Lepidoptera: Lasiocampidae).Enicospilusmauritii . 1♂ from Reunion ex Callopistriamaillardimaillardi (Guenée) (Lepidoptera: Noctuidae) feeding on Dryopterisbernieri (Pteridophyta: Dryopteridaceae) (idaceae) .Enicospilusluebberti . 1♂ from South Africa (SAMC SAM-HYM-P006196) ex Graphaniaatavistis (Hampson) (Lepidoptera: Noctuidae).Enicospilusbebelus Gauld & Mitchell, 1978. 1♂ from Central African Republic (SAMC SAM-HYM-P049492) and 1♀ from Gabon (SAMC SAM-HYM-P041707) with mesosoma interspersed with dark testaceous and black markings, and tergite 1 basally black; otherwise similar to original description.Enicospilusoculator Seyrig, 1935. 1♀ from Zimbabwe (SAMC SAM-HYM-P006232) with central sclerite totally absent, upper tooth twice as long as lower tooth, and numeric indices slightly different: FI 80%, AI 1.0, fore wing length 14 mm. Otherwise similar to PageBreakEnicospilusgrandiflavus Townes, 1973. 1♀ from South Africa (SAMC SAM-HYM-P049521) with entire head strongly darkened, nearly black. Otherwise similar to Enicospilusexpeditus . 1♀ 1♂ from South Africa (SAMC SAM-HYM-P054068) with hind tarsal claws less pectinate than figured in Enicospilusluebberti . Numerous specimens from South Africa , Bostwana (NMSA), and Kenya (BMNH) showed the following non-correlated variations: inter-ocellar area and metasomal apex yellowish-orange to totally black, antenna with 48–62 flagellomeres, longitudinal groove on mandible more or less impressed, proximal sclerite more or less elongate and central sclerite variously sclerotized. These variations encompass the definition of Enicospilusbatus Gauld & Mitchell, 1978, syn. n., described on a single specimen, which is hereby recognized as a junior synonym of Enicospilusluebberti.


Allergic rhinitis with/without conjunctivitis (AR/C) sufferers often rely on pharmacotherapy to relieve symptoms. Although the main goal of immunotherapy is long-term disease modification, reducing or eliminating the need for pharmacotherapy is also an important and desirable treatment goal.Ambrosia artemisiifolia; Merck/ALK-Abelló). Subjects with ragweed-pollen–induced AR/C were randomized ~16 weeks before the 2010 pollen season to once-daily MK-3641  or placebo. During the trial, all subjects, whether taking MK-3641 or placebo, could use AR/C rescue medication, including oral/ocular antihistamines and intranasal/oral corticosteroids. We examined rescue medication use in all groups.Data were pooled from two trials that evaluated the efficacy and safety of short-ragweed sublingual immunotherapy tablet (SLIT-T), MK-3641  subjects receiving MK-3641 12 Amb a 1-U and 144 of 324 (44.4%) subjects receiving 6 Amb a 1-U used no rescue medication over the entire ragweed season, compared with 109 of 340 (32.1%) subjects receiving placebo. These differences represented 56% and 38% improvements over placebo. Similarly, during the peak ragweed season 173 of 311 (55.6%) subjects and 161 of 317 (50.8%) subjects in the 12 Amb a 1-U and 6 Amb 1-U groups, respectively, reported no rescue medication use, in contrast to 136 of 333 (40.8%) subjects receiving placebo. Fewer subjects taking 12 and 6 Amb a 1-U  used oral antihistamine than those taking placebo; 35% and 28% fewer subjects used ocular antihistamine; and 43% and 27% fewer subjects used intranasal corticosteroid .Compared with placebo, the SLIT-T treatment MK-3641 reduced rescue-medication use among subjects with ragweed-pollen–induced AR/C.ClinicalTrials.gov Identifiers: NCT00783198; NCT00770315


Mevalonate kinase deficiency (MKD) is a rare autoinflammatory, autosomal-recessive defect on MVK gene. Clinical spectrum ranges from recurring febrile attacks to malformations and neurologic disorders. Gastrointestinal symptoms are cardinal. Severe gastrointestinal involvement has been described at the onset.To analyse severe gastrointestinal events (SGE) complicating MKD.Retrospective observational French cohort of MKD patients. SGE were defined as complicated inflammatory involvement, requiring an abdominal surgery and/or enteral/parenteral nutrition. Data were collected from clinical charts provided by the members of the Francophone Society for Paediatric Rheumatism and Inflammatory Diseases (SOFREMIP).25=13.7; P75=55.5); median MK activity: 2.2% . The significant co-morbidities found in SGE patients in comparison with the global cohort were: failure-to-thrive in 85.7% (6/7), pulmonary diseases in 37.5% (3/8) and feeding disorders in 28.6% (2/7) (p<0.05).From a 53-patient cohort, nine presented a SGE (17%). From these, disease onset median age was 1.0 months (0-12); one patient deceased (22 months) from a non-gastrointestinal event. Compound heterozygote mutations were found in 7/8, being Val377Ile the commonest (6/8). The main symptoms during febrile attacks were: diarrhoea , lymphadenopathy , skin lesions, joint pain , aphtous ulcers, abdominal pain , splenomegaly , hepatomegaly  and vomiting . Median mevalonic aciduria: 23.05 mmol/mol of creatinine , representing 43% (3/7) of patients with severe gastrointestinal disease: abdominal adhesions  and colitis/enterocolitis  were mainly found. 87.5% (7/8) needed surgery and 44.4% (4/9) required enteral/parenteral nutrition. Despite digestive resection, disease progression remained; two patients needed re-intervention due to surgical complications. Aphtous/ulcerative damage was the main endoscopic feature . The most consistent microscopic finding was lymphocytic infiltrates. IL-1 antagonists were the most used/effective treatment (4/9), resulting in with complete remission in all three patients with data available.MKD severe gastrointestinal involvement presentation has a non-negligible frequency. It usually appears as an aphtous/ulcerative disease involving any part of the digestive tract or as abdominal adhesions, frequently requiring surgery. The treatment with IL-1 antagonists resulted in complete remission in a majority of treated patients. Thus, MKD should be added to the list of monogenic early-onset inflammatory bowel disease.


Lactobacillus brevis BSO 464 was sequenced and assembly produced a chromosome and eight plasmids. This bacterium tolerates dissolved CO2/pressure and can rapidly spoil packaged beer. This genome is useful for analyzing the genetics associated with beer spoilage by lactic acid bacteria.The genome of brewery-isolate  Lactobacillus brevis BSO 464  can resist the headspace pressure and dissolved CO2 in packaged beer, making it a virulent beer-spoiler (–Brewery isolate -spoiler –3. Lb464De Novo assembler v2.5.3. Hawkeye (xl platform).Sequencing was performed using the Roche 454 FLX platform at the National Research Council Plant Biotechnology Institute . Two separate runs yielded 330,771 unpaired and 567,735 paired reads for ~30× coverage. Reads were assembled using Newbler GS L. brevis KB290  with nine plasmids .The Lb464 genome was assembled into a 2,503,991-bp circular chromosome (G+C content 45.7%) that had 8,461 bp cumulative of gaps due to transposase or repetitive regions not allowing PCR-based sequencing. Additionally, eight plasmids were assembled (G+C content ranged from 39.1% to 42.4%): pLb464-1 , pLb464-2 , pLb464-3 , pLb464-4 , pLb464-5 , pLb464-6 (5018 bp), Lb464-7 (2353 bp), and pLb464-8  (Pediococcus claussenii (hitA (horA (horC (Lb464 genome annotation by the NCBI PGAP pathway  producedaussenii , notablyii (hitA , horA (1tA (horA , and horrA (horC  on pLb46rA (horC . Based oLactobacillus brevis BSO 464 were deposited in GenBank under accession numbers CP005977, CP005978, CP005979, CP005980, CP005981, CP005982, CP005983, CP005984, and CP005985 for the chromosome and plasmids pLb464-1 to pLb464-8, respectively.The sequences for


NLRP3-gene encoding cryopyrin, leading to overproduction of IL-1β and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset, are generated in tumor, infective, and proinflammatory microenvironments and are capable of suppressing T cell responses. Consequently, MDSCs are considered a key intermediary in balancing innate and adaptive immune responses, particularly under chronic disease conditions.Muckle-Wells syndrome (MWS) is caused by mutations in the We hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in MWS.highCD66bhighIL-4RainterHLA-DRlow neutrophilic cells in the PBMC fraction, according to previously established human MDSC analysis methods. The functionality of MACS-isolated MDSCs was assessed using polyclonal T cell proliferation and cytokine/chemokine secretion tests. Physician's global assessment of disease activity, CRP, ESR, and T helper cell subsets were determined at the same time points and correlated with MDSC levels. Serum samples of 22 MWS patients and 5 healthy controls were examined by multiplex technique for possible MDSC inducing factors.We studied granulocytic MDSC numbers in 25 MWS patients under anti-IL-1 therapy with canakinumab and 20 healthy controls. After Ficoll density gradient sedimentation, granulocytic MDSCs were characterized as CD33p = 0.0025), although clinical MWS-disease activity was generally low at time of examination. MDSCs were functionally competent, as they suppressed polyclonal T cell proliferation, Th1, Th2, and Th17 responses. MDSCs correlated directly with Treg/Th17 and Treg/Th1 ratios indicating an influence on T helper cell subsets. Multiplex assays revealed the established MDSC-inducing growth factors GM-CSF and VEGF elevated in MWS sera even under anti-IL-1 therapy with canakinumab.MWS patients under anti-IL-1 therapy displayed significantly elevated MDSC numbers  compared to healthy controls (mean 0.45 ± 0.05%; range 0.12 - 1.04%; MWS patients under anti-IL-1 therapy display significantly elevated numbers of granulocytic MDSCs. Increased MDSCs in MWS might represent a novel autologous anti-inflammatory mechanism in autoinflammatory conditions and may serve as a future therapeutic target.N. Rieber Grant/Research Support from: NR, JKD, and DH obtained research grants from Novartis GmbH, Consultant for: NR and JKD took part in advisory boards for Novartis GmbH, A. Brand: None Declared, D. Neri: None Declared, T. Hall: None Declared, I. Schäfer: None Declared, S. Hansmann: None Declared, J. Kümmerle-Deschner: None Declared, D. Hartl: None Declared.


Pale-pink euhedral cobaltoan dolomite was associated with kolwezite [(Cu1.33Co0.67)(CO3)(OH)2] and cobaltoan malachite [2(CO3)(OH)2]. A crystal with a Co:Mg ratio of 1:5.6 (SEM/EDAX measurement), twinned on (11 -2 0) was used for crystal structural refinement. The refinement of the structural model of Reeder & Wenk  showed that Co is totally incorporated in the Mg site, with refined occupancy Mg0.83Co0.17, which compares with Mg0.85Co0.15 from chemical data. The Co substitution reflects in the expansion of the cell volume, with a pronounced increasing of the c cell parameter. A structural study has been undertaken on a cobaltoan dolomite, with chemical formula CaMgral. 1983, 68, 769 DOI: 10.1107/S2056989015003126/br2247Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989015003126/br2247fig1.tif. DOI: Micro photograph of the cobaltoan dolomite specimen, where pale pink cobaltoan dolomite is associated with pale green cobaltoan malachite.Click here for additional data file.10.1107/S2056989015003126/br2247fig2.tifx . DOI: x Cartesian rotation axis. Ca-centered octahedra are cyan, whereas Mg-centered octahedra are yellow; carbon and oxygen atoms are represented as green and red spheres, respectively.The crystal structure of cobaltoan dolomite, in a projection along [100], slightly tilted by 5° about along the Click here for additional data file.10.1107/S2056989015003126/br2247fig3.tif. DOI: Coordination polyhedra in cobaltoan dolomite. Displacement ellipsoids are drawn at the 50% probability.1049359CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Aeromonas hydrophila-like arabinose-negative isolates from diverse sources  sampled in Valencia (Spain) during 2004–2005, were characterized by 16S rRNA gene sequencing and extensive biochemical testing along with reference strains of most Aeromonas species. These isolates and all reference strains of A. hydrophila subsp. dhakensis and A. aquariorum showed a 16S rRNA sequence similarity of 99.8–100%, and they all shared an identical phenotype. This matched exactly with that of A. hydrophila subsp. dhakensis since all strains displayed positive responses to the Voges-Prokauer test and to the use of dl-lactate. This is the first report of A. hydrophila subsp. dhakensis recovered from environmental samples, and further, from its original isolation in India during 1993–1994. This was accurately identified and segregated from other clinical aeromonads  by using biochemical key tests. The API 20 E profile for all strains included in A. hydrophila subsp. dhakensis was 7047125. The prevalence of this species in Spanish sources was higher for water (9.4%) than for feces (6%) or eels (1.3%). Isolates recovered as pure cultures from diseased eels were moderately virulent (LD50 of 3.3×106 CFU fish−1) to challenged eels in experimental trials. They were all resistant to ticarcillin, amoxicillin-clavuranic acid, cefoxitin, and imipenem, regardless of its source. Our data point to A. hydrophila subsp. dhakensis as an emerging pathogen for humans and fish in temperate countries.Eight  Aeromonas (family Aeromonadaceae) is ubiquitous in aquatic ecosystems that include chlorinated drinking water, raw sewage, and natural waters  and free-living fish in such habitats  during 1993–1994 , A. hydrophila subsp. dhakensis exhibits high divergence from A. hydrophila subsp. hydrophila and A. hydrophila subsp. ranae  but 78 to 84% in the case of A. hydrophila subsp. dhakensis  in November 2004 ; and stry others .A. hydrophila subsp. dhakensis CECT5743, A. hydrophila subsp. dhakensis CECT5745, A. aquariorum MDC310, and A. aquariorum MDC317 was obtained by the Colección Española de Cultivos Tipo (CECT) service . Bacterial genomic DNAs were extracted according to a method described previously (Escherichia coli numbering]) (Escherichia coli numbering) (2 (100 mM), 1.0 μL dNTPs (10 mM each), 1.0 μL each forward and reverse primers (50 μM), 0.5 μL Taq polymerase  and 5.0 μL template DNA (50 ng μL−1) in a total volume of 50 μL. PCR amplifications of the DNA templates were performed using a PTC-100 ThermoCycler (MJ Research). The conditions for 16S rRNA gene amplification were (i) 4 min at 94°C; (ii) 30 cycles of 1 min at 94°C, 1 min 30 s at 52°C and 2 min at 72°C; and (iii) a final elongation step of 10 min at 72°C. Amplified products were examined by agarose gel electrophoresis (1.2%) and ethidium bromide staining. Purified amplicons (Mo Bio Laboratories) were sequenced by the dideoxy method using the BigDye Terminator v. 3.0 Ready Reaction cycle sequencing kit and analyzed in an ABI PRISM 3730 sequencer (Applied Biosystems). Sequencing primers were the same as those used in the amplification reaction but diluted tenfold (5 pmol).The almost complete 16S rRNA gene sequence of strains ABF132, ABF144, ABF145, MA17, MA26, MA131, 133.341, 133.343, CECT4588, eviously . UniversAeromonas , A. aquariorum , A. hydrophila subsp. hydrophila (CECT839T), A. veronii bv. veronii (CECT4257T), A. veronii bv. sobria (CECT4835), A. sobria (CECT4245T), A. jandaei (CECT4228T), A. popoffii (CECT4995), A. bestiarum (CECT4227T), A. allosaccharophila (CECT4199T), A. eucrenophila (CECT4224T), A. encheleia (CECT4342T), A. trota (CECT4255T), A. enteropelogenes (CECT4487T), A. caviae (CECT838T), A. media (CECT4232T), A. schubertii (CECT4240T), and A. diversa (CECT4254T) were examined in 45 tests described by us as valuable traits for identifying Aeromonas  were used in all isolates in order to know their API 20 E code.Minimal inhibitory concentrations (MICs) of kanamycin (K), tetracycline (TET), nalidixic (NA), oxolinic (OA) acid, flumequine (UB), erythromycin (ERY), rifampicin (RD) and chloramphenicol (CHL) were determined by the microbroth dilution method . In addi8, 107, 106, 105, 104, 103, 102, 101 CFU mL−1), or with 0.1 mL PBS (controls). Each set of six eels was kept in a 20 L aquarium under the following conditions: i) dechlorinated tap water, ii) water temperature around 20°C, iii) oxygen concentration in water was above 90% saturation, and iv) fish were not fed. Mortality was recorded daily for 10 days and was only considered if the challenged bacterium was recovered as pure culture from the internal organs.For the challenge experiment, six young eels of around 10–20 g were challenged by intraperitoneal injection with each of the bacterial doses , but that recovered from the ulcer was not  was calculated , FJ230076 (A. sanarellii A2-67T), FJ230077 (A. taiwanensis A2-50T), AJ508765 (A. hydrophila subsp. dhakensis LMG 19562T), X60408 (A. caviae NCIMB 13016T), X60415 (A. trota ATCC 49657T), AJ508766 (A. hydrophila subsp. ranae LMG 19707T), X60410 (A. media ATCC 33907T), X60404 (A. hydrophila subsp. hydrophila ATCC 7966T), S39232 , X60412 (A. sobria NCIMB 12065T), FJ976900 (A. rivuli WB4.1-19T), X60417 (Aeromonas sp. ATCC 35941T), AJ224308 (A. popoffii LMG 317541T), X60411 (A. eucrenophila NCIMB 74T), AJ224309 (A. encheleia CECT 4342T), AY532690 (A. molluscorum 848T), X60406 (A. bestiarum CIP 7430T), AF134065 , X60405 , X60407 , AB027544 , X74680 , FM999971 (A. piscicola S1.2T), X60413 (A. jandaei ATCC 49568T), AF170914 (A. culicicola MTCC 3248T), FJ230078 , X60414 (A. veronii bv. veronii ATCC 35624T), AJ536821 (A. simiae IBS S6874T), X60416 (A. schubertii ATCC 43700T), GQ365710 (A. diversa CECT 4254T).EU085557 . These were compared with those of A. hydrophila subsp. dhakensis LMG 19562T and A. aquariorum MDC 47T and with those from other Aeromonas-type strains , in accordance with that reported solely for the type strain of these species , using both simple matching (SSM) (J) coefficients. Moreover, they were all clearly segregated from the other type strains of the Aeromonas species whose phenotypic profile was included in the numerical analysis ; β-haemolysis of sheep red blood cells; and acid production from d-fructose, d-galactose, maltose, d-mannitol, d-mannose, sucrose, and d-trehalose; however, they all were negative for: Gram staining; production of brown diffusible pigment; susceptibility to O/129 (150 μg) (Oxoid discs); growth with 6% (w/v) NaCl; hydrolysis of urea; and acid production from d-amygdalin, dulcitol, d-fucose, meso-inositol, melibiose, d-raffinose, d-sorbitol, and d-xylose.The ng (SSM)  and Jaccanalysis . All str cluster  showed tA. hydrophila subsp. dhakensis-A. aquariorum” cluster exactly matched that described for A. hydrophila subsp. dhakensis  and -positive  simultaneously  and positive  for the utilization of dl-lactate   , which was obtained from Aeromonas strains  . Finally results  and 2. T strains . In addi jandaei , using b jandaei .Aeromonas hydrophila subsp. dhakensis was previously isolated in India (Aeromonas-positive samples was 17 (53.1%) and 20 (26.7%), respectively, with 32 patients suffering from Aeromonas gastroenteritis. The overall prevalence of A. hydrophila subsp. dhakensis in these Aeromonas-positive specimens was of 8.7% (6/69), although it was higher for water (17.7%) than for feces (6.25%) or eels (5%). Thus, we have found a wider distribution of A. hydrophila subsp. dhakensis in Spain in comparison with its unique previous finding in association with patients but not with water or fish (Aeromonas in these waters ranged from (102 to 104 CFU mL−1) in winter to (104 to 107 CFU mL−1) in summer , or by contact with them  were recovered from two siblings, a 1-year-old boy and a 6-year-old girl, who had acute gastroenteritis accompanied by bloody stools and high-grade (≥39°C) fever and required antibiotic treatment. The fact that these clinical isolates were rather multi-resistant to antibiotics   . Fortunaisolates , as alsoA. hydrophila subsp. dhakensis  which have been recovered from a wild European eel suffering from hemorrhagic septicemia . The present results constitute the first report of A. hydrophila subsp. dhakensis from a temperate country, suggesting the worldwide distribution of this species.In summary, species


HTLV-1 induces a persistent infection leading to an increased production of inflammatory cytokines. HIV, another retrovirus that causes systemic inflammation, is associated with atherosclerosis. However, few is known about HTLV-1-infection and atherosclerosis. To determine the prevalence and risk factors associated with atherosclerosis in patients infected with HTLV-1. a cross-sectional study involving 54 HTLV-1-infected patients (24 asymptomatic and 30 HAM/TSP), was carried out at the CHTLV between 2012 to 2013. Sociodemographic and cardiovascular risk factors were evaluated . Patients were submitted to Doppler echocardiography of both carotid and vertebral arteries to measure intimal-media layer. The association between intima-media thickness (IMT) and HAM/TSP diagnosis, HTLV-1 proviral load, low-density lipoprotrein cholesterol (LDL-c) or ultrasensitive C-reactive protein was determined. The mean age of patients was 57.1±12.3 years, 72.2% were women. Clinical atherosclerosis (IMT≥1.5mm) was found in nine patients (16.7%) and subclinical atherosclerosis (IMT>1 and <1.5) in 10 patients (18.5%). Atherosclerosis was more frequent in women (41%) compared with man (20%). Median age was significantly higher in patients with atherosclerosis . The mean of LDL-c level was 140.11±43.25 mg/dl (ranging from 49 to 287mg/dl). No significant differences were observed between the mean LDL-c level in individuals with subclinical (126.10±38.95mg/dl) and with atherosclerosis diagnosis (144.±43.87mg/dl), compared with individuals with normal IMT (143.21±44.65mg/dl), (p=0.4175). There was no correlation between HTLV-1 proviral load and IMT. No association was found between HTLV-1 infection and clinical or subclinical atherosclerosis as well as with the risk factors for cardiovascular diseases. A positive association between atherosclerosis and age was observed.


The LysE superfamily consists of transmembrane transport proteins that catalyze export of amino acids, lipids and heavy metal ions. Statistical means were used to show that it includes newly identified families including transporters specific for (1) tellurium, (2) iron/lead, (3) manganese, (4) calcium, (5) nickel/cobalt, (6) amino acids, and (7) peptidoglycolipids as well as (8) one family of transmembrane electron carriers. Internal repeats and conserved motifs were identified, and multiple alignments, phylogenetic trees and average hydropathy, amphipathicity and similarity plots provided evidence that all members of the superfamily derived from a single common 3-TMS precursor peptide via intragenic duplication. Their common origin implies that they share common structural, mechanistic and functional attributes. The transporters of this superfamily play important roles in ionic homeostasis, cell envelope assembly, and protection from excessive cytoplasmic heavy metal/metabolite concentrations. They thus influence the physiology and pathogenesis of numerous microbes, being potential targets of drug action. Rh. Rh20]. Using rigorous statistical criteria, we have expanded the LysE superfamily nearly four-fold. In addition to the LysE, RhtB and CadD families identified previously, this superfamily now includes the following families: NAAT, CaCA2, MntP, ILT, TerC, NicO, GAP and DsbD. Members of each of these families have been characterized and shown to play roles in transport of amino acids and resistance of heavy metal ions, along with cell surface maintenance. Most families include secondary carrier type transporters catalyzing heavy metal or amino acid efflux, but one family catalyzes amino acid uptake, another catalyzes heavy metal ion uptake, and a third catalyzes transmembrane electron transfer. GAP proteins have not been mechanistically characterized, but based on their inclusion in the LysE superfamily, we tentatively propose that GAP proteins operate as secondary carriers, where the energy source for lipid export is the proton motive force.Through sequence analyses, we were able to recognize a distinct pattern of homology. That is, LysE, RhtB, NAAT, CaCA2, MntP, ILT, TerC, NicO, GAP and DsbD proved to be homologous in 3 or more TMSs. The 3 TMSs that aligned are usually between the first 3 TMSs, the second 3 TMSs or both. This observation fits the predicted evolutionary pathway presented in According to the phylogenetic tree, amino acid exporter families RhtB and LysE branch close to each other, as suggested from previous studies . In contThis study suggests that members of the LysE Superfamily are involved in ionic homeostasis, protection from excessive cytoplasmic heavy metal/metabolite concentrations, cell envelope assembly and transmembrane electron flow. Many of the family members, however, are still poorly understood from functional and physiological standpoints. In continuing this project, genome context analyses will be conducted on members of each family. This will allow functional predictions, further promoting an understanding of the significance of these proteins. To date, no crystal structures exist for a member of this superfamily, and such studies will be crucial for understanding their mechanistic details. Thus, studies on the LysE superfamily remain in their infancy.S1 FigAlong with a step-wise description of the methods, the parameters for the programs used in major analyses are summarized.(TIF)Click here for additional data file.S2 Fig(A) LysE vs. RhtB. (B) RhtB vs. CadD. (C) LysE vs. CadD.(PDF)Click here for additional data file.S3 Fig(A) CadD vs. CaCA2. (B) LysE vs. CaCA2. (C) RhtB vs. CaCA2.(PDF)Click here for additional data file.S4 Fig(A) RhtB vs. MntP. (B) CadD vs. MntP. (C) CaCA2 vs. MntP.(PDF)Click here for additional data file.S5 Fig(A) CadD vs. ILT. (B) RhtB vs. ILT. (C) CaCA2 vs. ILT.(PDF)Click here for additional data file.S6 Fig(A) RhtB vs. TerC. (B) CadD vs. TerC. (C) LysE vs. TerC (D) MntP vs. TerC. (E) ILT vs. TerC. (F) CaCA2 vs. TerC.(PDF)Click here for additional data file.S7 Fig(A) LysE vs. NAAT. (B) RhtB vs. NAAT. (C) CadD vs. NAAT (D) MntP vs. NAAT. (E) TerC vs. NAAT.(PDF)Click here for additional data file.S8 Fig(A) RhtB vs. NicO. (B) CadD vs. NicO. (C) TerC vs. NicO (D) NAAT vs. NicO.(PDF)Click here for additional data file.S9 Fig(A) RhtB vs. GAP.(PDF)Click here for additional data file.S10 Fig(A) RhtB vs. DsbD. (B) CaCA2 vs. DsbD. (C) MntP vs. DsbD. (D) NAAT vs. DsbD. (E) GAP vs. DsbD.(PDF)Click here for additional data file.S11 Fig(A) LysE. (B) RhtB. (C) CadD. (D) CaCA2. (E) MntP. (F) NAAT. (G) NicO. (H) GAP. (I) DsbD. (J) ILT. (K) TerC.(PDF)Click here for additional data file.S12 FigGSAT comparisons between TMS#1–3 and TMS#4–6 for three CaCA2 homologues with assigned UniProt accession numbers. (A) Q2JWH3. (B) I7M883. (C) K4DX00.(PDF)Click here for additional data file.S13 FigGSAT comparisons between TMS#1–3 and TMS#4–6 for three ILT homologues with assigned UniProt accession numbers. (A) Q8YX33. (B) K9Q6B8. (C) J2KV33.(PDF)Click here for additional data file.S14 FigGSAT comparisons between TMS#1–3 and TMS#4–6 for three MntP homologues with assigned UniProt accession numbers. (A) A8SU47. (B) R9SLI6. (C) C6JCY1.(PDF)Click here for additional data file.S15 FigGSAT comparisons between TMS#1–3 and TMS#4–6 for three TerC homologues with assigned UniProt accession numbers. (A) A4IKQ1. (B) G8M4S7. (C) R9LI44.(PDF)Click here for additional data file.S16 Fig(A) LysE. (B) RhtB. (C) CadD. (D) CaCA2. (E) MntP. (F) ILT. (G) TerC. (H) NAAT. (I) NicO. (J) GAP. (K) DsbD.(PDF)Click here for additional data file.S17 Fig-20 by BLAST (Using UniProt) for each query sequence to improve the accuracy of aligning a small number of distantly related sequences. The bootstrap values are shown in blue text and located near each node.The Mafft-homologs function was set to retrieve 200 homologs at a threshold E-value of 1e(TIF)Click here for additional data file.S18 Fig(PDF)Click here for additional data file.S19 Fig(PDF)Click here for additional data file.S20 Fig(PDF)Click here for additional data file.S21 Fig(PDF)Click here for additional data file.S22 Fig(PDF)Click here for additional data file.S23 Fig(PDF)Click here for additional data file.S24 Fig(PDF)Click here for additional data file.S25 Fig(PDF)Click here for additional data file.S26 Fig(PDF)Click here for additional data file.S27 Fig(PDF)Click here for additional data file.S28 Fig(PDF)Click here for additional data file.S29 FigThe tree was generated using the SuperFamilyTree program and viewed using FigTree. It depicts the evolutionary relationship between the 11 different families in this study. Clustering indicates closer phylogenetic relationships. The tree is based on tens of thousands of BLAST bit scores generated with the SFT1 program where every protein was compared with every other protein included in the analysis. The SFT2 program was used to integrate all of the information to show the relationships of the eleven families to each other. Bootstrap values have been added in blue text and located near each node.(TIF)Click here for additional data file.S1 Supporting InformationThe corresponding zip file contains the FASTA files generated using Protocol1, for comparisons with Protocol2.(ZIP)Click here for additional data file.S2 Supporting InformationThe corresponding zip file contains the multiple sequence alignment (MSE) outputs generated using ClustalX, Mafft, and ProbCons. These MSEs have been used to generate (ZIP)Click here for additional data file.S3 Supporting InformationThe corresponding zip file contains the 100 trees generated from SFT, the consensus tree, the FASTA sequences used to generated the trees, and the newick file for the best tree generated from RAxML analyses (described in (ZIP)Click here for additional data file.S4 Supporting InformationThe corresponding zip file contains the FASTA files used to conduct MEME Suite analyses shown in Figs (ZIP)Click here for additional data file.S5 Supporting InformationThe corresponding PDF file contains the (PDF)Click here for additional data file.S6 Supporting InformationThe corresponding PDF file contains the (PDF)Click here for additional data file.S7 Supporting InformationThe corresponding PDF file contains the (PDF)Click here for additional data file.


Thromboembolic complications (TEC) are very common and lethal in patients suffering from traumatic injury . The trat test, univariate and multivariate logistic regression analyses were performed.A retrospective chart review (2010 to 2013) was conducted on adult trauma patients that were admitted into a level 1 Trauma Centre in Toronto. Demographics, date of PTP initiation, date of TEC diagnosis (CT-PE/US Doppler), injury type and severity were collected. A comparison between early and late PTP initiation has been made with regards to TEC development. Student's P < 0.0005), had lower ISS , shorter length of stay (LOS) , more pelvic fractures , more head injury , less blunt trauma , lower incidence of TEC (5.3% (44) vs. 8.5% (42), P = 0.023), and lower mortality rate (1.5% vs. 7.5%). Univariate analysis showed LOS (P < 0.0005), ISS (P < 0.0005), time to PTP initiation (P = 0.0018) and blunt MOI (P = 0.0099) significantly associated with TEC events. Multivariate analysis, however, showed TEC events correlated only to LOS (P = 0.0001). Stepwise multiple logistic regression confirmed LOS as independently associated with TEC events .A total of 1,312 patients received PTP, 821 (62.5%) initiated early PTP (within 48 hours) while 491 (37.5%) initiated after 48 hours. The group that initiated early prophylaxis was younger (mean: 46 vs. 55, Mortality rates in patients with delayed PTP are higher. Our study shows LOS as the only independent predictor for TEC. However, this might not necessarily reflect causation. Delayed PTP appears not to be an independent predictor to TEC events in trauma patients, which favours current clinical trends when it comes to contraindicating early PTP initiation.


A single-bolus non-ECG-triggered method was previously proposed to reduce the complexity of quantitative myocardial perfusion imaging . CompareData was acquired continuously with no ECG-triggering. 26 projections per slice were acquired following each SR-preparation in an interleaved manner. HYPR was used to reconstruct images with 5-fold undersampling. A sliding window was used to produce series of low resolution images in the basal slice with a temporal resolution of 44 ms. Triggering signal was derived retrospectively from the mean signal intensity in an ROI drawn around the heart. AIF was estimated using single-cardiac cycle T1 mapping [nd study, another 12 healthy volunteers underwent stress-rest studies using the proposed method. Mean myocardial perfusion reserve (MPR) was compared with previously published values.Ten healthy volunteers underwent rest perfusion MRI on a Siemens 3T Verio. A dual-bolus protocol was performed using a conventional clinical Cartesian sequence for comparison [Mean MBF values found using the ECG-triggered dual-bolus method and the non-ECG-triggered integrated T1 mapping method were 0.82 ± 0.21 and 0.76 ± 0.13 ml/min/g, respectively. There was no significant difference (p = 0.45) between them. The mean rest and stress MBF and MPR was 0.86±0.5, 3.91±1.1 ml/min/g, and 4.31±1.3, respectively.A 3-slice, non-ECG-triggered, single-bolus quantitative perfusion MR method with integrated T1 mapping for AIF measurement produces similar MBF as the reference dual-bolus method with comparable ventricular coverage. Mean MPR is similar to those reported in literature. The proposed non-ECG-triggered technique improves ease-of-use, and has the potential to improve robustness to arrhythmias. This method may improve the clinical feasibility of quantitative myocardial perfusion imaging.NIH grant numbers T32 EB51705 and RO1 EB002623, NIBIB grant number EB002623, AHA Scientist Development Grant 14SDG20480123, GCRC grant MO1-RR00425, and Edythe L. Broad Women's Heart Research Fellowship UN55ES6580F.


Moderate-to-severe allergic rhinitis (AR) is often poorly controlled. Patients remain symptomatic on treatment, despite multiple therapies. A more effective treatment is needed. We assessed the efficacy of MP29-02*  and fluticasone propionate (FP) in an advanced delivery system) during different seasons and for different symptoms and severities vs AZE, FP or placebo (PLA).Four thousand and twenty two moderate/severe SAR patients (≥12 yrs) were randomized into 4 double-blind, PLA-controlled, 14-day, parallel-group trials to MP29-02*, AZE, FP or PLA nasal sprays (1 spray/nostril bid), during the Texas mountain cedar (MP4001), Spring (MP4002), Autumn (MP4004) and Spring/Summer (MP4006) seasons. Overall change from baseline (CFB) in reflective total nasal symptom score (rTNSS) was the primary endpoint. It was assessed by severity post-hoc in 2 ways . CFB in individual nasal and ocular symptom scores was also assessed.The response to MP29-02* was consistent across seasons; mean CFB -5.5, -5.5, -5.6 and -5.6 in each study (p<0.001 vs PLA). Nasal symptom relief was significantly greater with MP29-02* than with FP or AZE in all studies. In study MP4001 MP29-02 was approx. twice as effective as FP (relative difference (RD) 47%; p=0.0031) and 3 times as effective as AZE . For less severe AR (defined by median baseline rTNSS) the RD to MP29-02* was 42% vs FP (p=0.0188) and 64% vs AZE (p=0.0002), increasing to 49% and 70% vs FP (p=0.0436) and AZE (p=0.0035), respectively for more severe AR. When severity was categorized according to median baseline RQLQ the RD to MP29-02* was 60% vs FP (p=0.0244) and 69% vs AZE (p=0.0068) for those with less severe AR compared to 49% vs FP (p=0.0194) and 64% vs AZE (p=0.0013) for those with more severe AR. MP29-02* provided superior relief from all nasal and ocular symptoms than AZE or FP, which was particularly evident for congestion  & ocular itching .MP29-02* provides consistently superior symptomatic relief to an intranasal antihistamine or topical corticosteroid in AR patients regardless of season, symptom or severity, supporting MP29-02 as the drug of choice for AR.*Dymista


Erythropoietin treatment could augment the immune response and could be a tiger for systemic lupus erythematous flare-up and increasing the activity of renal and systemic lupus.Anemia is a common clinical finding in end-stage renal failure (ESRD). Systemic lupus erythematous (SLE) is an important cause of chronic kidney disease and anemia in lupus nephritis has different and complex causes, including; anemia of chronic disease (ACD), autoimmune hemolytic anemia (AHA), iron deficiency anemia (IDA), pure red cell aplasia (PRCA), pernicious anemia (PA), myelofibrosis, hemophagocytic histiocytic syndrome, thrombotic microangiopathy and drug induced myelotoxicity . Combina3/µl  and reticulocyte was 1%. Also, platelets count; 156×103/µl, serum creatinine: 7.63mg/dl, BUN: 84 mg/dl, uric acid: 7.5 mg/dl, phosphorous: 5.8 mg/dl, calcium: 8.4 mg/dl. Serum complements were as follow: C3: 68 mg/dl (90-180), C4: 10 mg/dl (10-40) and CH50: 76% (90-98). Further laboratory tests revealed; anti MPO–ANCA (IgG): 0.8 u/ml , Anti PR3-ANCA(IgG): 6.0 U/ml , Anti-dsDNA: 42 U/ml, LDH: 800 IU/ml (< 500 ), AST: 36 IU/ml, ALT: 38 IU/ml (<40), serum Na: 139 meq/l, serum K: 5, 0 meq/l, total bilirubin: 0.33 mg/dl (0.1-1.2), direct bilirubin: 0.09 mg/dl (0.1-0.4). Antiphospholipid antibody (IgG/IgM) was negative. Stool examination was negative for occult blood. Also upper gastrointestinal endoscopy had normal results. Peripheral blood examination revealed a large number of teardrop red blood cells. Bone marrow aspiration was unsuccessful (dry tap), bone marrow biopsy was compatible with myelofibrosis. Renal allograft biopsy revealed diffuse lupus nephritis (lupus nephritis class IV) with cellular crescents. This situation was difficult to make a decision to start an intensive immunosuppressive therapy in the presence of marrow failure. Despite receiving adequate dialysis and blood transfusion and adjusted immunosuppressive therapy her general condition worsened and died two months after the admission.We recently admitted a 23 year-old-female with advance renal failure and oliguria. Physical examination on admission revealed a blood pressure of 130/90 mmHg and pulse rate of 105 minute/min. Cardiac examination showed a loud systolic murmur. Abdominal examination disclosed a palpable spleen. Hemodialysis was started with temporary jugular vein catheter. Laboratory examination revealed; hemoglobin: 4.1 g/dl, hematocrit: 17%, MCV: 78.6 fl, MCH: 24.4 pg/cell and MCHC: 31.1 g/dl. White blood cell count: 3.6×10In SLE, there is an association between the level of inflammatory cytokines and intensity of anemia. Inflammatory cytokines inhibit erythropoietin production and erythroid progenitor cells proliferation. In severe cases, inflammatory cytokines lead to myelofibrosis ,2. RenalMRA is the single author of this paper.No financial support by any institution.None to declare.


From 1999–2002 to 2009–2012, the prevalence of diabetes increased for non-Hispanic black and Mexican American adults, but remained stable for non-Hispanic white adults, increasing the disparity with the two minority populations. In 1999–2002, the prevalence of diabetes among non-Hispanic black (14.0%) and Mexican American (13.9%) adults aged ≥20 years was 1.6 times the prevalence among non-Hispanic white adults (8.5%). By 2009–2012, diabetes prevalence among Mexican American adults (20.5%) had increased to more than twice the prevalence among non-Hispanic white adults (9.1%); among non-Hispanic black adults (17.9%), the prevalence had increased to nearly twice that among non-Hispanic white adults.Source: Health, United States, 2014: with special feature on adults aged 55–64. Table 44. Available at http://www.cdc.gov/nchs/hus.htm.Reported by: Sheila J. Franco, sfranco@cdc.gov, 301-458-4331; Shilpa Bengeri.


Doubts on the efficacy of exercise treatment for adolescents with Idiopathic Scoliosis (IS) still exists.To verify the effectiveness of exercises in everyday clinics.Prospective observational controlled cohort study nested in a prospective database started in March 2003.Setting: outpatient tertiary referral clinics.Participants: consecutive patients from start of the database to 31/12/2010. Inclusion criteria: IS; Risser 0-2; 11° to 20° Cobb; age 10 years or more; first evaluation. Exclusion criteria: consultations only; immediate prescription of a brace.Groups: Physiotherapic Specific Scoliosis Exercises - SEAS school ; Controls (CON: less than 15 min/week); Usual Physiotherapy (UP: other institutes/protocols).End-Of-Treatment (EOT): medical prescription, bracing, Risser 3.Failures: bracing for scoliosis; EOT above 30°.Statistical analysis: intent-to-treat (ITT: drop-outs included as failures) and efficacy (EA: only EOT patients). Relative Risk of failure (RR), 95% Confidence Interval (CI), and clinical and radiographic changes have been calculated.Out of 327 patients, 34 (10%) were excluded due to bracing at first evaluation. We included 293 adolescents: 145 PSSE, 95 UP, 53 CON, with no differences at baseline. Physicians prescribed bracing (failure) without differences among groups.Failures and drop-outs were 84 (28.7%) and 47 (16.0%) respectively: 21.4% and 18.6% in PSSE; 33.7% and 9.5% in UP; 39.6% and 20.8% in CON.Efficacy analysis (RR): CON vs PSSE 1.90 (IC 1.48-2.33); UP vs PSSE 1.42 (1.01-1.82); CON vs UP: not significant.Intent-to-treat (RR): CON vs PSSE 1.51 (1.21-1.80); CON vs UP 1.40 (1.08-1.72); UP vs PSSE: not significant.At the end of exercises, aesthetics (TRACE) improved statistically in PSSE (1.8 points out of 12) and UP (1.5), not in CON; only PSSE improvement was statistically better than CON.Patients performing UP or nothing (CON), compared to those treated with PSSE (SEAS), increase the risk of failure (bracing and/or 30° at EOT) 1.9 and 1.4 times respectively (EA).


Evidence of the association between vitamin D, insulin resistance and oral disposition index (oDI) in obese children and adolescents is limited. We investigated serum 25(OH) D levels in obese children and adolescents in Zhejiang, China, and determined the relationship between serum 25(OH) D and glucose metabolism.A cross-sectional design was used. All together 348 obese and 445 non-obese children and adolescents (aged from 6-16 years old) were enrolled in this study. Obese children were divided into four subgroups: normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and ITG (IFG+ITG) according to the oral glucose tolerance test. We measured serum 25(OH) D levels and calculated the homeostasis model of insulin resistance (HOMA-IR), the whole body insulin sensitivity index (WBISI), the product of β-cell function and insulin sensitivity by the disposition index (DI).The levels of 25(OH)D in obese group were significantly lower than those of non-obese group; serum 25(OH)D level in obese with NGT group was higher than that of the other three subgroups, and it was significantly inversed with LogHOMA-IR , positively correlated with LogWBISI, LogHOMA0DI after control for age, sex, season, puberty stage . Obese patients with vitamin D deficiency have a significantly higher risk of disturbing the glucose metabolism, such as IFG, ITG, IFG plus ITG, either IFG or ITG, for its OR 3.198(95%CI 1.467-6.97), 5.443(95%CI 1.863-15.897), 5.560(95%CI 1.212-25.502), 4.007(95%CI 2.017-7.962).25(OH) D deficiencies or insufficiency are common in obese children and adolescents in Zhejiang, China. Obese patients with 25(OH) D deficiency (<30nmol /L) are at higher risk for abnormal glucose metabolism.


This study determined the effects of eight weeks of heavy resistance training combined with branched-chain amino acid (BCAA) supplementation on body composition and muscle performance.Nineteen non-resistance-trained males resistance-trained (3 sets of 8-10 repetitions) four times/week for eight weeks while also ingesting 9 g/day of BCAA or 9 g/day of placebo (PLAC) on exercise days only . Data were analyzed with separate 2 x 2 ANOVA (p < 0.05).For total body mass, neither group significantly increased with training (p = 0.593), and there also were no significant changes in total body water (p = 0.517). Also, no training- or supplement-induced (p = 0.783) changes occurred with fat mass or fat-free mass (p = 0.907). Upper-body (p = 0.047) and lower-body strength (p = 0.044) and upper- (p = 0.001) and lower-body muscle endurance (p = 0.013) were increased with training; however, these increases were not different between groups (p > 0.05).When combined with heavy resistance training for eight weeks, 9 g/day of BCAA supplementation, half given 30 min before and after exercise, had no preferential effects on body composition and muscle performance.


Mycobacterium abscessus complex, the third most frequent mycobacterial complex responsible for community- and health care-associated infections in developed countries, comprises of M. abscessus subsp. abscessus and M. abscessus subsp. bolletii reviously referred as Mycobacterium bolletii and Mycobacterium massiliense. The diversity of this group of opportunistic pathogens is poorly described.M. abscessus complex genomes found a pan-genome of 6,153 proteins and core-genome of 3,947 (64.1%) proteins, indicating a non-conservative genome. Analysing the average percentage of amino-acid sequence identity (from 94.19% to 98.58%) discriminates three main clusters C1, C2 and C3: C1 comprises strains belonging to M. abscessus, C2 comprises strains belonging to M. massiliense and C3 comprises strains belonging to M. bolletii; and two sub-clusters in clusters C2 and C3. The phylogenomic network confirms these three clusters. The genome length (from 4.8 to 5.51-Mb) varies from 5.07-Mb in C1, 4.89-Mb in C2A, 5.01-Mb in C2B and 5.28-Mb in C3. The mean number of prophage regions (from 0 to 7) is 2 in C1; 1.33 in C2A; 3.5 in C2B and five in C3. A total of 36 genes are uniquely present in C1, 15 in C2 and 15 in C3. These genes could be used for the detection and identification of organisms in each cluster. Further, the mean number of host-interaction factors  varies from 70 in cluster C1, 80 in cluster C2A, 74 in cluster C2B and 93 in clusters C3A and C3B. No significant differences in antibiotic resistance genes were observed between clusters, in contrast to previously reported in-vitro patterns of drug resistance. They encode both penicillin-binding proteins targeted by β-lactam antibiotics and an Ambler class A β-lactamase for which inhibitors exist.In-depth analysis of 14 published M. abscessus complex comprises three genomospecies, corresponding to M. abscessus, M. bolletii, and M. massiliense. The genomics data here reported indicate differences in virulence of medical interest; and suggest targets for the refined detection and identification of M. abscessus.Our comparative analysis indicates that The online version of this article (doi:10.1186/1471-2164-15-359) contains supplementary material, which is available to authorized users. Mycobacterium abscessus was long confused with Mycobacterium chelonae[Mycobacterium salmoniphilum[Mycobacterium immunogenum[Mycobacterium massiliense[Mycobacterium bolletii[Mycobacterium franklinii[Mycobacterium chelonae-abscessus complex. This complex is the third most frequent mycobacterial complex infecting humans in developed countries besides the Mycobacterium tuberculosis and Mycobacterium avium complexes [M. salmoniphilum[The non-tuberculous mycobacterium  chelonae. Other coniphilum, Mycobacmunogenum, Mycobacssiliense, Mycobac bolletii and Mycoranklinii altogethomplexes , 8. Biblomplexes . Not onlomplexes , 11 and omplexes –14 are ioniphilum, 15.M. abscessus comprises two subspecies named M. abscessus subsp. abscessus and M. abscessus subsp. bolletii. Later taxon accommodates isolates previously referred as M. bolletii or M. massiliense[M. abscessus and M. bolletii, it shares 99% sequence identity with M. massiliense. RpoB gene sequencing founded the description of recent species [M. massiliense from M. bolletii. In this report, the previous nomenclature M. abscessus, M. bolletii and M. massiliense forming the M. abscessus complex, has been retained for clarity.Current nomenclature is that the species ssiliense. This no species –19 but y species –22. Mult species  and mult species  differenM. abscessus, 13 M. massiliense and two M. bolletii genomes in the National Center for BioInformatics (NCBI) genome database provides new opportunities to assess the diversity of this species. Here, we review 14 complete published M. abscessus complex genomes and compare them with the re-annotated M. tuberculosis H37Rv genome  includes M. abscessus type strain and strains M93, 94, M152 and Go06; cluster 2 (C2) contains two subclusters: cluster 2A (C2A) includes M. massiliense type strain and strains M154 and M18; cluster 2B (C2B) includes strains 47 J26, M115, M172 and M139; cluster 3 (C3) includes two subclusters: cluster 3A (C3A) includes M. bolletii type strain and cluster 3B (C3B) includes M. bolletii strain M24 (Table The average percentage of amino-acid sequence identity (AAI) of core proteins was determined as previously described . The AAIM. abscessus complex proteomes were further aligned using Mauve software [M. abscessus differently from the whole genome concatenated tree   and BLASC1 strains have been isolated from American and Malaysian patients suffering knee infection and lower respiratory infection, respectively , M. massiliense (C2) and M. bolletii (C3). Using an AAI <97% threshold would further determine two subspecies in M. massiliense (C2A and C2B) and in M. bolletii (C3A and C3B). Recent whole genome sequencing analyses of clinical isolates in Great Britain also clearly distinguished three clusters in agreement with the three here reported [M. abscessus complex, to recognize three genomospecies M. abscessus (C1), M. bolletii (C2), and M. massiliense (C3); and four unnamed subspecies C2A, C2B; C3A, C3B.Altogether, genomics analyses revealed a more heterogeneous structure of abscessus. It has abscessus, 35. Thereported . All theM. abscessus median GC% content is 64.2%, ranging from 62.7% (M. abscessus ATCC 19977) to 64.2% (strain Go 06). The GC% is not characteristic of the clusters as the median GC% content of C1, C2A and C3 is 64.2%, close to the median 64.1% GC% content in C2B.M. abscessus M154) to 5.51-Mb (M. abscessus M24) with a median of 5.07-Mb. The median of genome size is 5.07-Mb in C1, 4.89-Mb in C2A, 5.01-Mb in C2B and 5.28-Mb in C3. Differences in the genome size correlate with the number of prophage regions which are detected in 13/14 M. abscessus genomes  has the smallest genome encoding no prophage whereas M. bolletii M24 (C3) has the largest genome encoding seven prophage regions  and phage tape measure protein. Both ends of this region encode putative phage integrases. M. abscessus genomes encode small prophage-like regions. However, only M. bolletii has been reported to produce a mycobacteriophage that we named Araucaria after we recently resolved its electron microscopy 3D structure [M. abscessus M94 genome harbours one particular pseudo-tRNA spanning the region 51,150-57,394 in contig 33, which is not observed in the other M. abscessus genomes [M. abscessus however, no such genes were identified but phages could be targeted for the differentiation between the three M. abscessus genomospecies.However, there is a significant 14.7% variation in the genome length from 4.8-Mb  genes conferring resistance to tetracyclyine and doxycycline; the number of tet(M) genes was correlated to the resistance to cyclines in Escherichia coli[M. massiliense was reported to be susceptible and M. abscessus and M. bolletii to be resistant to doxycycline [M. abscessus genomes encode resistance to fusidic acid, glycopeptides, MLS (Macrolide-Lincosamide-StreptograminB), phenicols, rifampicin, sulphonamide and trimethoprim. Also, M. abscessus genomes encode FolP homologs conferring resistance to cotrimoxazole, homolog of UDP-N- acetylglucosamine 1-carboxyvinyltransferase, a MurA protein conferring resistance to fosfomycin and homologs of 23S rRNA methylases conferring resistance to macrolides. Also, M. abscessus genome encodes an erm(41) gene which mutations were reported to confer clarithromycin resistance [In-vitro tests showed that M. massiliense clinical isolates could be distinguished from M. abscessus isolates for their susceptibility to ciprofloxacin [M. bolletii isolates were reported to be resistant to all quinolones [M. abscessus exhibiting high resistance to ciprofloxacin [M. abscessus mycobacteria encode qepA2, a plasmidic gene conferring quinolone resistance in gram-negative bacteria [M. abscessus mycobacteria were reported to be in-vitro resistant to penicillin, amoxicillin, cefoxitin, ceftriaxone, cefotaxime and imipenen [M. abscessus genomes encode an Ambler class A β-lactamase homologous to β-lactamases in gram-negative bacteria and to two β-lactamases in M. tuberculosis. β-lactamases inhibitors have not been evaluated against M. abscessus sensu lato mycobacteria.As all mycobacteria, sistance –44. M. aproteins ; and a msistance . M. abscsistance , 47. Indchia coli. Howeverycycline . M. abscsistance . In-vitrfloxacin  whereas inolones . A mutatfloxacin . This obfloxacin . Accordibacteria . M. abscimipenen . This coimipenen , 55. M. M. abscessus are ubiquitous environmental organisms in soil and water [M. chelonae, M. abscessus, M. massiliense and M. immunogenum were reported to survive within Acanthamoeba polyphaga tropohozoites and cysts [M. abscessus genomes encode factors implicated in host interactions. The mean number of genes encoding proline-glutamate (PE), proline-proline glutamate (PPE), 10-kDa lipoprotein antigen precursor (LpqH), Mammalian Cell Entry (MCE), oxidoreductase (Yrbe) and type VII secretion system is of 70 in C1, 80 in C2A, 74 in C2B and 93 in C3. In M. abscessus, rough colonies lack mmpL4 (a gene required for glycopeptidolipid biosynthesis) and lost surface colonization, replication into human macrophages and stimulation of innate immune response; these observations suggested that glycopeptidolipid was a virulence factor [M. avium subsp. avium[M. abscessus genomes encode MCE proteins similar to M. tuberculosis H37Rv. MCE operon promotes internalization of M. tuberculosis by mammalian cells [mce operons which correlated with pathogenicity [M. abscessus genomes encode 12 (C1) to 21  copies of Yrbe proteins. As for secretion systems, recent evidences showed that mycobacteria evolved specialized type VII secretion systems to transport extracellular proteins across the cell wall [M. tuberculosis[M. abscessus, our analyses indicate that ESX-3 and ESX-4 systems are conserved  lacks two proteins of the ESX-3 system and M. abscessus M93 (C1) lacks ESAT-6 like and CFP-10-like proteins secreted by the ESX-4 system. Interestingly, M. abscessus M18 (C2A) encodes ESAT-6 and CFP-10 proteins secreted by ESX-1 system. In addition, there are two or three PE and six  to 12 (M. bolletii M24) PPE proteins, which are reported to be involved in the virulence of M. tuberculosis[Actinobacteria  and pseudomonas (Pseudomonas aeruginosa and Burkholderia cepacia). Although distantly related, these bacteria share the same ecosystem as M. abscessus within cystic fibrosis microbiota.nd water  where thnd cysts . Accordie factor –58. Accoe factor  and biofe factor . Glycopesp. avium. M. abscan cells  and initan cells . The numgenicity , varies ell wall . Type VIerculosis, 66. In erculosis. Our anaM. abscessus has a non-conservative genome, suggesting the possibility of on-going transfer of additional genetic material. Unsurprisingly, M. abscessus has already acquired antibiotic resistance. Also, phages have mediated diversity and horizontal gene transfer which drived the rapid evolution of this complex. Indeed, gene transfers have driven the evolution of M. abscessus towards three different genomospecies M. abscessus, M. massiliense and M. bolletii; and the evolution of four different yet unnamed subspecies. Each genomospecies has its own specificities in terms of genome size, prophagome and genome content. We identified 66 genes uniquely present in each genomospecies; these genes could be used in refined detection and identification of M. abscessus organisms. These genomic differences support differences in host interactions and the clinical presentation of infection with M. massiliense (C2A and C2B) being more virulent than the two other genomospecies. Host-interaction factors may contribute to the ability of M. abscessus to colonize mammalian hosts where its respiratory tract habitat put it in close proximity to other serious opportunist pathogens which can act as donors of additional host-interaction factors.Our in-depth genomic analyses indicate that M. abscessus genomespecies will help understanding their pathogenesis factors and could reveal new, more specific targets for drug design and diagnosis tools.Here reported informations regarding differences between M. abscessus strains were downloaded from Genbank (Table The whole genomes of 14 http://www.uniprot.org/), the Clusters of Orthologous Groups (COG) [Protein sequences were predicted using prodigal software  to generps (COG)  and a hoM. abscessus homologous genes using orthoMCL [Proteome sequences were compared using by BlastP and pairwise alignments using ClustalW and the ANI was determined by the mean percentage of nucleotide sequence identity of core proteins . We clusorthoMCL  on the tM. abscessus proteomes were aligned using Mauve software [software  to infersoftware . The ortsoftware . Using tsoftware .http://treebase.org/treebase-web/home.html) repository, under the accession URL http://purl.org/phylo/treebase/phylows/study/TB2:S15632.The data set of Figure http://purl.org/phylo/treebase/phylows/study/TB2:S15632?x-access-code=6fa2ebc53b96e3ae412a8df19187ab41&format=html.Reviewer access URL: The data sets of Figure The data sets of Figure A-AlignedM. abscessusgenome matrix constructed using Mauve software to infer phylogeny using the Neighbor-Net algorithm in the package SplitsTree4. B- The matrix of binary discrete characters  constructed using the orthologous group data found by orthoMCL to infer phylogeny using the Neighbor-Net algorithm in the package SplitsTree4. (XLS 28 KB)Additional file 1: The matrix used for Heatmap clusterisation ofMycobacterium abscessustype VII secretion system compared toMycobacterium tuberculosisH37Rv. (XLS 26 KB)Additional file 2:


Coinfection in patients with SARS-CoV-2 has been associated with greater complications. We describe the clinical characteristics and outcomes of 126 pediatric patients with COVID-19 and viral, bacterial, or fungal coinfection.We retrospectively reviewed and analyzed electronic data of all pediatric patients who tested positive for SARS-CoV-2 from April 16, 2020, to April 15, 2022, in our center. Confirmation of COVID-19 was based on positive RT-PCR. Viral coinfections (VC) were identified using a multiplex RT-PCR respiratory viral panel, bacterial coinfection (BC) was determined by positive bacterial culture  or clinical/radiological manifestations and antimicrobial assessment by a pediatric Infectious Diseases expert and fungal coinfection (FC) diagnosis based on Consensus definitions of invasive fungal disease.During the study period, among 400 pediatric patients with COVID-19, 126 children had coinfection. Children >10 years were the most affected age group. Underlying disease was present in 69%, hematological malignancies were the most common (17.5%). BC was detected in 76.9% (n=97), bacterial pneumonia (54.6%) was the main diagnosis, followed by oncologic patients with initial febrile neutropenia and posterior SARS-CoV-2 detection . Unusual BC as congenital syphilis w detected; acute appendicitis was the initial presentation of COVID-19 in 8 patients. VC was identified in 15.87% (n=20), prevailing rhinovirus (9.5%) and adenovirus (3.96%), One FC presented as proven pulmonary aspergillosis (0.8%). B-V and B-F coinfection were detected in 2 patients. Fever and cough were the most common symptoms, higher fever >40°C was mostly observed in the BC group (3%). Twenty-seven patients with BC (27.8%) were admitted to intensive care, with the OR 0.7 IR 95% (0.611–1.008), 4.1% died. One ICU admission was observed in the VC group (5%) and all VC cases resolved without complications.Pediatric patients with COVID-19 coinfection, especially BC were common in our center representing nearly one-third of the infected children, including unusual coinfections. BC was identified as a risk factor for ICU admission OR 0.7 IR 95% (0.611–1.008). Favorable outcomes were observed in most cases.All Authors: No reported disclosures.


Bloodstream infection (BSI) following arterial aneurysm repair may signify vascular graft infection (VGI). The incidence of BSI and its implications in patients with arterial grafts have received scant attention with limited contemporary study. Therefore, the aim of the current investigation is to describe the incidence and epidemiology of BSI following arterial aneurysm repair in a population-based cohort.>18 years) residing in eight counties in southern Minnesota between January 1, 2010 and December 31, 2020. All repairs were performed at Mayo Clinic Rochester. Electronic health records were screened for initial BSI episode following aneurysm repair and complicating VGI.Retrospective case-cohort study using the expanded Rochester Epidemiology Project (e-REP) to identify all arterial aneurysm repairs performed in adults  overall, including 18.2 (95% CI 11.9-26.7) following open surgical repair and 10.2 (95% CI 5.8-16.6) following endovascular repair (p=0.148). Thirty-nine (92.9%) of the BSI cases were monomicrobial, with 18 (46.2%) due to Gram-positive organisms and 21 (53.8%) due to Gram-negative organisms. Of the 42 patients with BSI, 10 (23.8%) had VGI. VGI occurred in 8/18 (44.4%) monomicrobial Gram-positive BSI as compared to 2/21 (9.5%) monomicrobial Gram-negative BSI (p=0.013). The 3-year mortality rate following BSI was 52.3%.There was no statistically significant difference in incidence rates of BSI following open surgical repair and endovascular repair. Higher rates of VGI were seen with Gram-positive BSI as compared to Gram-negative BSI.Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties.


E. coli belonging to the serotype O177 is a rare strain found in ruminants, especially cattle. When compared to shiga toxin producing E. coli (STEC) O157 and non-O157 STEC  serotypes, the antimicrobial resistance, virulence factors, and genomic structure of E. coli O177 are poorly understood. Therefore, in this article, we present the whole genome sequence data of two aEPEC E. coli O177 isolates (E. coli O177_CF-154-A and E. coli O177_CF-335-B) generated using Illumina MiSeq platform. The raw data were generated, cleaned, and assembled using Trimmomatic and SPAdes. Genome data analysis yielded 5,112,402 and 5,460,435 bp, comprising contigs 101 and 191 with GC contents of 50.7% and 50.5% for E. coli O177_CF-154-A and E. coli O177_CF-335-B, respectively. Prokaryotic Genome Annotation Pipeline (PGAP) and Rapid Annotation using Subsystem Technology (RAST) showed that the complete genome of E. coli O177_CF-154-A contained 5040 coding sequences (CDS), 5146 genes, 4896 proteins, 90 RNAs, and 78 tRNA while that of E. coli O177_CF-335-B contained 5463 CDS, 5570 genes, 5230 proteins, 92 RNAs, and 80 tRNA for. A total of 426 and 425 subsystem features with 5190 and 5662 CDS were obtained for E. coli O177_CF-154-A and E. coli O177_CF-335-B, respectively. Several genes encoding virulence and antimicrobial resistance were identified in both genomes. Complete genome sequence data of both isolates have been deposited in the National Center for Biotechnology Information (NCBI), GenBank: accession numbers, VMKH00000000 (E. coli O177_CF-154-A) and VMKG00000000 (E. coli O177_CF-335-B). This data can be used as a reference for determining the virulence and antimicrobial resistance in E. coli O177 isolates from different sample sources.Atypical enteropathogenic  Moreover, these data give an extensive information on the virulence and antimicrobial resistance profile of this serotype, which may contribute to understanding and improving of scientific knowledge of this pathogenic strain.These data provide genomic features of •E. coli O177 serotype from different environmental samples. In addition, these data can be used in public health to establish policy framework and strategy intended to curb antimicrobial resistance, especially in humans.The data may be used by researchers to develop new methods for detection of •This genome can be used as a reference, especially for comparative genomic and epidemiological studies.1E. coli O177 isolates (E. coli O177_CF-154-A and E. coli O177_CF-335-B) were obtained from cattle faeces in the North West province, South Africa (−27° 00′ 0.00″ S 26° 00′ 0.00″ E), E. coli O177_CF-154-A and E. coli O177_CF-335-B) are summarised in E. coli O177_CF-154-A and E. coli O177_CF-335-B, respectively. There were 5040 coding sequences (CDS), 5146 genes, 4896 proteins, 90 RNAs, and 78 tRNA for E. coli O177_CF-154-A genome, while E. coli O177_CF-335-B genome contained 5463 CDS, 5570 genes, 5230 proteins, 92 RNAs, and 80 tRNA. Furthermore, both genomes contained 2 CRISPR Arrays. Based on RAST annotation, there were 426 and 425 subsystem feature counts with 5190 and 5662 CDS in E. coli O177_CF-154-A and E. coli O177_CF-335-B, respectively. As depicted in Two atypical enteropathogenic 22.1E. coli O177 isolates were obtained from Antimicrobial Resistance and Phage Biocontrol Laboratory, Department of Microbiology. The isolates were selected based on the virulence and antimicrobial resistance profiles as described in the previous studies Two atypical enteropathogenic 2.2TM-Tissue MiniPrep Kit  following the manufacturer's instructions. The DNA concentration was determined using the NanoDropTM-Lite 1,000 spectrophotometer . After fragmentation, DNA libraries were constructed using the Nextera XT DNA library prep kit  following the manufacturer's instruction. The fragmented DNA was amplified using 12 cycles PCR, which adds the index sequences [index 1 (i7) and index 2 (i5)]. The PCR products were purified using 0.6 × Agencourt AMPure XP beads (Beckman Coulter), and the quality was determined using 1.5% (w/v) agarose gel. Each library was diluted to 12 pmol. Samples were normalized to 4 nM using Nextra XT Library Normalization Beads (Illumina). Normalized libraries were pooled and 150 base paired-ends sequencing was performed with MiSeq Reagent V3 600-cycle kits on the Miseq instrument (Illumina).Genomic DNA was extracted from overnight cultures using the Zymo Research Genomic DNA2.3de novo genome assembly was carried out using SPAdes (v.3.13) 4  with all parameters  set at default Raw sequence data were generated and FASTQ files were obtained. The data were assessed for quality using FASTQC (v.0.11.5) and filtered for low quality reads and adapter regions using Trimmomatic (v.0.36) This study did not involve the use of human subjects or animal experiments.Peter Kotsoana Montso: Conceptualization, Methodology, Data curation, Writing – original draft, Visualization, Investigation, Software, Validation, Writing – review & editing. Victor Mlambo: Conceptualization, Methodology, Supervision, Software, Validation, Writing – review & editing. Collins Njie Ateba: Conceptualization, Methodology, Supervision, Software, Validation, Writing – review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Inonotus hispidus (Bull.: Fr.) P. Karst (IH) is an edible and medicinal parasitic mushroom. In this study, after a systematic analysis of its nutritional ingredients, the regulatory effects of IH on lipid metabolism were investigated in mice fed a high-fat diet (HFD). In HFD-fed mice, IH reversed the pathological state of the liver and the three types of fat and significantly decreased the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and leptin (LEP) and increased the level of high-density liptein cholesterol (HDL-C) in serum. Meanwhile, IH ameliorated liver damage by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels in the liver and serum. Compared with HFD-fed mice, IH significantly modulated the gut microbiota, changed the relative abundances of microflora at different taxonomic levels, and regulated lipid levels. The results showed that 30 differential lipids were found. Results from Western blotting confirmed that IH regulated the nuclear factor erythroid-2 related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway and oxidative stress. This study aimed to provide experimental evidence for the applicability of IH in obesity treatment.Obesity is frequently associated with dysregulated lipid metabolism and lipotoxicity.  Obesity is a pathological condition requiring clinical intervention ; it may Obesity is frequently associated with dysregulated lipid metabolism and lipotoxicity , which mGrifola frondosa modulates ceramide levels and restores lipid metabolism by inhibiting the Toll-like receptor 4/NF-κB signaling associated with inflammation and insulin resistance (IR) to treat obesity [Inonotus hispidus (Bull.: Fr.) P. Karst (IH) is an edible and medicinal parasitic mushroom belonging to the phylum Basidiomycota, class Agaricomycetes, and family Hymenochaetaceae. IH is mainly distributed in the Hebei Chengde, Shandong Linqing, Xiajin, and Xinjiang Aksu areas, and it prefers to live on mulberry, water willow, elm, poplar, and Japanese acacia. Previous investigations on IH have mainly focused on chemical composition analysis, artificial cultivation, mycelium fermentation, and pharmacological activity studies [Currently, weight loss occurs primarily through diet- and exercise-related strategies, which are often not sustainable . Bariatr obesity . Inonotu studies ,17,18,19 studies . IH petr studies . Extrace studies . HoweverIn this study, based on the detection of the main components of IH, combined with gut microbiota and lipid metabolomic analyses, the role of IH in regulating oxidative stress and inflammation, based on the Nrf2/NF-κB signaling pathway, to alleviate obesity symptoms was explored in C57BL/6 mice with DIO. Our data provide experimental evidence for the applicability of IH in obesity treatment.IH fruiting bodies from Linqing, Shandong, were identified by Professor Yu Li. The general components , twenty kinds of amino acids, thirty-five kinds of fatty acids, seven kinds of minerals, six kinds of heavy metals, eight kinds of vitamins, and five kinds of nucleotides in IH were systematically detected, as we previously described ,23.n = 6/group), including an intragastrically HFD-fed group with 5 mL/kg of normal saline, an intragastrically simvastatin (SV) -treated group with 3 mg/kg of SV, and low- and high-dose intragastrically IH-treated groups with 500 and 1000 mg/kg of IH, respectively, daily for 8 weeks. The NCD mice were randomly divided into two groups (n = 6/group), including the vehicle-treated intragastrically NCD-fed group with 5 mL/kg of normal saline and the intragastrically IH-treated NCD-fed group with 500 mg/kg of IH daily for 8 weeks. Weekly measurements of body weight and plasma glucose levels were performed for all mice. After 8 weeks of drug treatment, the mice were euthanized using CO2 (the CO2 replacement rate was 30–70% of the container volume per minute). Peripheral blood was obtained by sampling the retro-orbital venous plexus. Organs , epididymal white adipose tissue (eWAT), inguinal white adipose tissue (iWAT), and perirenal white adipose tissue (pWAT) were dissected and weighed. The above tissue parts were stored at −80 °C for further biochemical analysis, and the remaining parts were fixed in a 4% tissue fixative  for subsequent pathological analysis.All experiments were performed in accordance with the guidelines of the Institutional Animal Ethics Committee of Jilin University (SY202106003). Thirty-six male C57BL/6JGpt mice (5 weeks old) from GemPharmatech Co., Ltd.  were maintained on either a normal chow diet  or a high-fat diet  under specific-pathogen-free (SPF) conditions on a 12 h light/dark cycle at a constant temperature (23 ± 1 °C) and humidity (40–60%) for 8 weeks. To establish the DIO model for the high-fat diet study, 24 randomly selected mice were fed an HFD ad libitum during the entire experimental period. From week 9, the DIO mice were randomly divided into four groups . Serum was collected twice by centrifugation at 3500 rpm at 4 °C for 10 min. The levels of alanine aminotransferase (ALT) (MM-44625M1), aspartate aminotransferase (AST) (MM-44115M1), IL-1β (MM-0040M1), IL-6 (MM-0163M1), TNF-α (MM-0132M1), and plasminogen activator inhibitor-1 (PAI-1) (MM-0066M1) in the liver and serum, ROS (MM-43700M1), malondialdehyde (MDA) (MM-0897M1), and lysophosphatidylcholine (LPC) (MM-44698M1) in the liver, and high-density liptein cholesterol (HDL-C) (MM-44105M1), low-density lipoprotein cholesterol (LDL-C) (MM-43685M1), total cholesterol (TC) (MM-0632M1), triglycerides (TG) (MM-0631M1), and leptin (LEP) (MM-0622M1)  in the serum were measured using enzyme-linked immunosorbent assay (ELISA) kits.Liver tissue was homogenized in normal saline, and the protein concentration was determined using a Pierce™ bicinchoninic acid (BCA) Protein Assay Kit  staining and Oil Red O staining were performed as described in our previous study . Fixed an = 3/group) was performed by 16S rRNA sequencing using an Illumina NovaSeq platform at Shanghai Personalbio Technology Co., Ltd. , as described in our previous study [A gut microbiota analysis of mouse cecum content in samples from NCD-, HFD-, and IH-treated groups (500 mg/kg) (us study . Sequencn = 3/group) was performed by liquid chromatography–mass spectrometry (LC–MS) at Shanghai Personalbio Technology Co., Ltd. , as described in our previous study [p ≤ 0.05) in metabolite levels and variable importance in projection (VIP) values ≥ 1.0 were regarded as the standard for differential lipids to filter out biomarkers.A plasma lipidome analysis of mouse serum from the NCD-, HFD-, and IH-treated groups (500 mg/kg)  buffer  containing protease and phosphatase inhibitors  and were homogenized using a high-throughput tissue grinder . After denaturation, 40 μg of protein was separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)  and then transferred onto a polyvinylidene fluoride (PVDF) membrane . Membranes were blocked by Rapid Closure solution  and incubated with the primary antibodies overnight and then the secondary antibodies for 4 h at 4 °C. Finally, immunoreactive bands were visualized using an automated chemiluminescence image analysis system  and Ultra High Sensitivity enhanced chemiluminescence (ECL) kits . Protein expression levels were measured using ImageJ software  and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Details regarding the antibodies used in this work are presented in p < 0.05.All values are presented as means ± SD. Biochemical indices were compared between different groups by one-way analysis of variance (ANOVA) followed by Tukey’s test using BONC DSS Statistics 25 . Differences were considered statistically significant at The general nutritional composition of IH is 45.90% total dietary fiber, 25.50% total sugar, 15.90% protein, 9.90% ash, 9.22% total flavonoids, 6.18% moisture, 5.04% total polyphenols, 4.70% fat, 1.48% total triterpenes, 0.50% total saponins, 0.46% total alkaloids, 0.31% total sterols, etc. Among them, the total dietary fiber content was the highest. The glutamic acid content was the highest among the 20 amino acids detected. Seven minerals, including calcium (Ca), iron (Fe), zinc (Zn), selenium (Se), potassium (K), sodium (Na), and manganese (Mn), were detected, in addition to low concentrations of six heavy metals (lead (Pb), arsenic (As), mercury (Hg), cadmium (Cd), copper (Cu), and chromium (Cr)). Eight vitamins and five nucleotides were also detected . The corp < 0.05) (p < 0.05) (p < 0.001) (p < 0.01) (p < 0.01) (p < 0.05) (p < 0.05) (p < 0.001) without affecting other organs  A. Compar < 0.05) B and sup< 0.001) C, TC (p  < 0.01) D, and TG < 0.01) E in seru < 0.05) F. H&E st < 0.05) G. Among  < 0.05) . Compare < 0.05) . IH signr organs . IH alonr organs .p < 0.001) (p < 0.001) (p < 0.001) (p < 0.001) (p < 0.001) (p < 0.05) (p < 0.05). In the serum of HFD-fed mice, IH and SV showed the same effects on AST (p < 0.05) (p < 0.05) (p < 0.001) (p < 0.01) (p < 0.05) (p < 0.01) (p < 0.05). IH failed to influence the serum levels of ALT , high degrees of lipid deposition, and large amounts of lipid droplets (H&E staining) were improved by IH and SV A. Moreov< 0.001) B, AST (p< 0.001) C, IL-1β < 0.001) D, IL-6 (< 0.001) E, and TN< 0.001) F in the  < 0.05) G in HFD- < 0.05) I, IL-6 ( < 0.05) K, TNF-α < 0.001) L, and PA < 0.01) M. At 500 < 0.05) J and PAI < 0.01) M in HFD-s of ALT H. IH alos of ALT B–M.Allobaculum, Adlercreutzia, Shigella, Dorea, Oscillospira, and Streptococcus and decreased Ruminococcus and Coprobacillus compared with the vehicle-treated HFD-fed mice  (p < 0.01)  D. IH and < 0.01) E.p < 0.01) (p < 0.05) (p < 0.001), IKKα + β (p < 0.001), and IκBα  and significantly upregulated the expression levels of Nrf2 (p < 0.001), HO-1 (p < 0.01), and SOD-1 . Compared with the vehicle-treated NCD-fed mice, IH alone only increased the levels of Nrf2 (p < 0.01) and HO-1 (p < 0.05) and suppressed the activation of P-IκBα (p < 0.001) (The hepatic levels of ROS ( < 0.01) A and MDA < 0.05) B were de< 0.001) C.IH is rich in dietary fiber, which helps to improve hyperlipidemia by affecting lipid metabolism  and has Allobaculum, Dorea, and Oscillospira, facilitating the production of short-chain fatty acids (SCFAs) related to metabolic processes [Ruminococcus and Coprobacillus. SCFAs such as acetate, propionic acid, and butyric acid can reduce the generation of pro-inflammatory cytokines [Allobaculum can regulate hepatic lipid metabolic processes [Allobaculum plays a role in suppressing inflammatory responses by reducing the expression of p-IKK and TNF-α [Dorea is negatively associated with inflammatory diseases [Oscillospira and Ruminococcus are inflammatory bacteria associated with inflammatory bowel disease [Oscillospira helps to maintain lipid homeostasis [Rosa Roxburghii Tratt, possessing hypolipidemic effects, can reduce the abundance of Coprobacillus [Streptococcus may be the main force for decomposing a large amount of cellulose [In obese mice, IH increased the abundance of the genera rocesses ,34,35 whytokines , displayytokines . SCFAs cytokines ,39. Dietytokines , which hytokines , Allobacrocesses , shows arocesses , and itsrocesses . Allobacnd TNF-α , which hnd TNF-α , Dorea idiseases . Both Os disease ,48, and eostasis . Rosa Robacillus . Moreoveellulose , which iellulose . Meanwhiellulose ,54, and ellulose .Metabolites of intestinal flora affect the process of lipid metabolism and host lipid composition . IH coulSOD and HO-1 [HO-1, a key target gene of Nrf2, exerts antioxidant effects by resisting endogenous and exogenous stimuli [Oxidative stress leads to increased lipid peroxidation and is closely associated with hyperlipidemia-related tissue damage ,63. Nrf2and HO-1 . SOD-1 iand HO-1 . HO-1, a stimuli . Nrf2/HO stimuli .Oxidative stress and inflammation are inextricably associated . Nrf2 caThe present study had certain limitations. In this study, we first reported the hypolipidemic effects of IH and analyzed the components involved. However, the specific active components possessing hypolipidemic activity were not confirmed; thus, further investigation is needed.In conclusion, IH regulated lipid metabolism through the Nrf2/NF-κB signaling pathway, which is closely related to oxidative stress and inflammatory responses, in HFD-fed mice. Our study provides insights into the application of IH as a hypolipidemic agent and will facilitate its commercial application.


In: Public health round-up. Bull World Health Organ. 2022 May 1; 100(5):296–297, on page 297, middle column, the second sentence should read as follows: “As of 15 March, a total of 53 people were reported with suspected Yellow fever infections, six of whom died of the disease .”https://dx.doi.org/10.2471/BLT.22.010522Public health round-up. Bull World Health Organ. 2022 May 1;100(5):296–297.