Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results.

INTRODUCTION: We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. MATERIAL AND METHODS: Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. RESULTS: Twenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (-5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01). Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DISCUSSION: Our results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

Staphylococcus aureus related to bovine mastitis in Switzerland: Clonal diversity, virulence gene profiles, and antimicrobial resistance of isolates collected throughout 2017.

Staphylococcus aureus can be associated with subclinical, acute, chronic, and toxic cases of bovine intramammary infections, leading to considerable financial losses for the dairy industry in Switzerland and worldwide. In addition, milk products are one of the most common food categories implicated in staphylococcal food poisoning in humans. Detailed information on the population structure, as well as the virulence and resistance characteristics of Staph. aureus originating from bovine mastitis milk is needed to allow for source attribution and risk assessment of Staph. aureus in a food poisoning context and to improve therapeutic approaches in cattle. Our objective was to assess the population structure, phenotypic resistance patterns, and virulence and resistance gene profiles of Staph. aureus isolates from bovine mastitis milk in Switzerland. To this end, 58 Staph. aureus strains were characterized. The DNA microarray was used to test for the presence or absence of virulence and resistance genes. In addition, minimum inhibitory concentrations of various antimicrobial agents were determined by microdilution. To assess the population structure of the isolates, we determined clonal complexes (CC) using DNA microarray hybridization profiles and performed multilocus sequence typing and spa typing. The strains were assigned to 7 clonal complexes, 10 sequence types, and 11 spa types, with CC705 (43%), CC97 (33%), and CC20 (12%) representing the most common lineages and t529 (43%) and t267 (21%) representing the most common spa types. Only 1 isolate was assigned to CC8, a clonal lineage linked to high within-herd prevalence of mastitis. A total of 14% (n = 8) of strains were classified as resistant to penicillin, and 1 strain each was classified as oxacillin and pirlimycin resistant. Although no clinical breakpoints are available for the combination of kanamycin/cefalexin, growth of all strains was inhibited by the lowest combination of kanamycin/cefalexin concentrations tested (4 µg/mL of kanamycin and 0.4 µg/mL of cefalexin). One strain assigned to CC20, ST389, and t2094 exhibited resistance to penicillin, oxacillin, and pirlimycin as well as intermediate susceptibility to erythromycin and high minimum inhibitory concentration for several antimicrobial agents, for which no breakpoints were available.

Effect of sorafenib combined with cytostatic agents on hepatoblastoma cell lines and xenografts.

BACKGROUND: Sorafenib has recently been shown to reduce tumour growth in hepatoblastoma (HB) xenografts. The effect of a combined administration with cytostatic agents was now investigated. METHODS: Cell viability after treatment with sorafenib and different cytostatic agents was evaluated in two HB cell lines (HUH6 and HepT1) using MTT assay. ERK signalling was investigated by western blot, NOXA expression by rt-PCR, and formation of DNA adducts using immunocytology. NMRI mice bearing subcutaneous HUH6-derived tumours were treated with sorafenib alone or in combination with cisplatin. Tumour progression, viability, apoptosis, and vascularisation were monitored by tumour volume, AFP levels, TUNEL assay, and CD31 immunostaining, respectively. RESULTS: The combination of sorafenib and cisplatin led to a remarkable decrease in cell viability. The cisplatin-induced enhanced ERK1/2 activation, but not NOXA expression and the formation of DNA adducts was partly abrogated by sorafenib. In HB xenografts, both, sorafenib and alternated application of sorafenib and cisplatin significantly reduced tumour growth (P<0.05). Levels of AFP were lower in both treated groups (P=0.08). Relative apoptotic areas were increased (P=0.003). Mean vascular density was the lowest in the sorafenib/CDDP group (P=0.02). CONCLUSION: The combination of sorafenib with cisplatin might be a promising treatment option for high risk or recurrent HB.

The effect of ventral nerve cord severance and male castration on female mating behavior, clutch size, and maternal care in the ring-legged earwig.

Mating is critical for the expression of oviposition and maternal care in the earwig, Euborellia annulipes; additionally, mating diminishes receptivity to additional mating and promotes a decline in juvenile hormone synthesis at the end of the gonadotrophic cycle (in contrast to most insect species wherein mating stimulates juvenile hormone production). We report here that severance of the ventral nerve cord of virgin females similarly promoted egg deposition and maternal care of eggs, diminished mating receptivity, and elicited a timely decline in juvenile hormone biosynthesis. Mating of intact females to adult males that were castrated as larvae did not abolish oviposition; however, clutch size was reduced, and no eggs developed. Such castrated males had smaller seminal vesicles than did intact males, presumably attributable to lack of sperm in castrated males. In contrast, mating of intact females to males castrated on day 1 of adult life did not reduce clutch size compared with those of sham-operated animals and did not abolish fertilization; in fact, these castrated males produced viable offspring after six matings. These results are consistent with the notion that ventral nerve cord severance mimicked mating in intact animals. Following mating, the ventral nerve cord likely is a conduit to release the brain from inhibiting oviposition and maternal care. The presence of sperm in the spermatheca is not necessary for release of this inhibition but may modulate clutch size.

Fracture-embolization of duromedics valve prosthesis and microscopic uncommon lesions.

We report a sudden leaflet fracture of a Duromedics mitral valve 6 years after implantation. The patient had cardiogenic shock and complained of asthenia, orthopnea, and tachycardia. Transesophageal echocardiography showed the lack of one leaflet of the prosthesis and regurgitation. An emergency mitral replacement was successfully performed. Angiographic computed tomography scan localized the sequestrum that embolized the common iliac arteries. Examination of the deficient prosthesis showed multiple lesions and, in particular, a subsurface lesion that may be characteristic of carbon pyrolytic valves.

The Lui elution technique. A simple and efficient method for eluting ABO antibodies.

The Lui elution and the heat elution techniques are the most simple techniques available for eluting antibodies from red cells. Both are very effective for eluting ABO antibodies. We compared the two techniques and found the Lui technique superior in that it more efficiently eluted ABO antibodies, required less hands-on time, and allowed more flexibility in the procedure. We therefore recommend the Lui elution technique as the method of choice for eluting ABO antibodies, especially for the evaluation of hemolytic disease of the newborn.

[Sociologic studies in acne vulgaris. 1. Disease significance of acne vulgaris]. / Soziologische Untersuchungen bei der Acne vulgaris. 1. Uber den Krankheitswert der Acne vulgaris.

A questionnaire was presented to 2009 18--19 year old military recruitment candidates which enabled assessment of antipathy towards patients with severe acne vulgaris, the occupational handicap associated with severe acne and subjective inhibitions in acne patients. In addition, these persons were examined clinically with regard to presence of acne vulgaris. Finally, the level of education of the persons questioned was determined. The investigations show that severe acne has an appreciable disease rating. This results from antipathy of other people, the occupational inpediment and the psychological inhibitions of the acne patient. This disease rating appears to be objectively greater the lower the level of education of the acne patient. The disease rating does not appear to be entirely clear to the acne patient with a low level of education.

[Sociological studies in acne vulgaris. 2. Effect of the disease on the evaluation of clinical picture and motivation for therapy]. / Soziologische Untersuchungen bei der Acne vulgaris. 2. Uber den Einfluss der Erkrankung auf die Beurteilung des Krankheitsbildes und die Motivation zu einer Therapie.

A questionnaire was presented to 2009 18--19 year old recruitment candidates. The questionnaire enabled appraisal of antipathy towards patients with severe acne vulgaris and the occupational inpediment of severe acne. It was shown in comparison of patients with clinically relevant acne and healthy subjects or patients with a minor variant of acne that acne patients are more prepared to tolerate other acne patients than are healthy subjects. A questionnaire which enabled appraisal of attitudes to therapy was presented in addition to 351 patients with clinically relevant acne in this collective. The schools attended were also recorded in these patients. It was shown that the motivation to undergo treatment can be assumed in only half of the acne patients; this motivation is less the more radical the therapy. However, the motivation is greater the higher the educational level of the person questioned.