Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by robust effects in patients with high IL-22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in patients with AD.

The potential use of Bacillus anthracis as a weapon of mass destruction poses a threat to humans, domesticated animals, and wildlife and necessitates the need for a rapid and highly specific detection assay. We have developed a real-time PCR-based assay for the specific detection of B. anthracis by taking advantage of the unique nucleotide sequence of the B. anthracis rpoB gene. Variable region 1 of the rpoB gene was sequenced from 36 Bacillus strains, including 16 B. anthracis strains and 20 other related bacilli, and four nucleotides specific for B. anthracis were identified. PCR primers were selected so that two B. anthracis-specific nucleotides were at their 3 ends, whereas the remaining bases were specific to the probe region. This format permitted the PCR reactions to be performed on a LightCycler via fluorescence resonance energy transfer (FRET). The assay was found to be specific for 144 B. anthracis strains from different geographical locations and did not cross-react with other related bacilli (175 strains), with the exception of one strain. The PCR assay can be performed on isolated DNA as well as crude vegetative cell lysates in less than 1 h. Therefore, the rpoB-FRET assay could be used as a new chromosomal marker for rapid detection of B. anthracis.Bacillus anthracis is a causal agent of anthrax, a serious and often fatal infection of livestock and humans. It is considered one of the most effective biological weapons of mass destruction because of its highly pathogenic nature and spore-forming capability and has attracted attention due to its potential use as a biological warfare agent (2). This bacterium can infect humans by cutaneous, gastrointestinal, or respiratory routes. The standard laboratory method of identification takes advantage of the lytic nature of the B. anthracis-specific gamma bacteriophage (9). Anthrax bacilli are often distinguished on the basis of time-consuming morphological or phenotypic characteristics, such as gram-positive staining, spore-forming capability, nonhemolytic reaction on sheep blood agar, sensitivity to penicillin, nonmotile nature, and inability to ferment salicin (11). B. anthracis is distinguished from the other members of the closely related Bacillus cereus group of bacteria by the presence of the toxin-encoding pXO1 (19, 24) and capsule-encoding pXO2 plasmids (14,23,34). Both plasmids are needed for virulence; thus, the absence of either plasmid results in attenuation.B. anthracis, Bacillus thuringiensis, B. cereus, and Bacillus mycoides, are members of the B. cereus group of bacilli. These closely related bacteria are pathogens of mammals (B. anthracis and B. cereus) and insects (B. thuringiensis). The B. cereus group is one of the most taxonomically ambiguous group of bacilli (27). In fact, DNA-DNA hybridization (30) and pulsedfield gel electrophoresis (15) have shown great homology among B. anthracis, B. thuringiensis, and B. cereus. A recent multilocus enzyme electrophoresis study has concluded that the members of this group belong to one species (16)....

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A multicentre, randomised, double blind treatment trial was set up comparing imipramine (a tricyclic antidepressant with anticholinergic action), mianserin (a quadricyclic antidepressant without anticholinergic activity), and placebo, (a) possibly to identify an effective alternative drug and (b) to elucidate the action of imipramine in enuretic children. Eighty children (65 boys, 15 girls) aged 5-13 years, wet three or more nights a week, were studied. Exclusions were a urinary tract infection or abnormality, other organic illness, or severe emotional disorders. After a four week assessment, 25 children were randomised to eight weeks' treatment with imipramine 25 mg, 26 to mianserin 10 mg and 29 to placebo, followed by four weeks without treatment. Dry nights and a wetness score were recorded throughout.During treatment, imipramine was superior to both placebo and mianserin (p < 0.001) in achieving dry nights and reducing wetness scores. It led to a definite improvement in 72% of children. Mianserin produced a mildly beneficial effect that was not superior to placebo. No side effects were recorded.Mianserin would not be a satisfactory alternative treatment for nocturnal enuresis. The efficacy of imipramine is unlikely to be the result of its antidepressant activity. (Arch Dis Child 1996;75:62-66) Keywords: nocturnal enuresis, mianserin, imipramine. Imipramine has been used effectively,"4 although it may cause side effects when the dosage is increased and a relapse may follow cessation of treatment. It also carries a risk of accidental poisoning if swallowed by younger siblings, 5 although this is now infrequent. The mechanism of action of imipramine is uncertain and has been attributed variously to a central antidepressant effect, or anticholinergic action, or to a direct effect on the bladder trigone. 4 In view of the need for a safe and effective alternative to imipramine, an international multicentre, randomised, double blind therapeutic trial was set up involving centres in Finland, the Netherlands and Britain, comparing the effects of the tricyclic antidepressant imipramine, a quadricyclic antidepressant mianserin, and placebo. The dual objective was to search for a possible alternative drug treatment with a sustained response and to explore the mechanism of action of imipramine by comparing two effective antidepressant drugs, only one of which, imipramine, has additional anticholinergic activity. The results are presented in 80 children studied in the British centres: Southampton, Leeds, and Aberdeen. Southampton and MethodsThe protocol of the study is outlined in fig 1 and was approved by each ethical committee. RECRUITMENTChildren aged 5-13 years with nocturnal enuresis, bed wetting at least three nights a week, were recruited. (One child was included who had an earlier very wet record but who had an average of only 2.5 wet nights a week in the preceding four weeks.) The history was taken, a full clinical examination including height, weight, and blood pressure was carried out and a Rutter A ...