Multicenter Evaluation of the Novel ETEST Fosfomycin for Antimicrobial Susceptibility Testing of Enterobacterales, Enterococcus faecalis, and Staphylococcus Species.

Fosfomycin is a phosphonic acid derivative active against a wide spectrum of Gram-positive and Gram-negative pathogens. It is used for the treatment of uncomplicated urinary tract infections (uUTI) or severe infections by oral or intravenous (i.v.) administration. In order to improve its performance and robustness, the fosfomycin strip, an antibiotic gradient diffusion strip, was redeveloped and evaluated in the multicenter study summarized in this paper. ETEST fosfomycin (ETEST FO) clinical performance was evaluated by three study sites on 152 Enterococcus faecalis, 100 Staphylococcus spp. and 330 Enterobacterales in comparison with the CLSI and EUCAST agar dilution reference method. Referring to FDA performance criteria, the ETEST FO achieved 91.0% of essential (EA) and 99.0% of categorical agreement (CA) for Escherichia coli. In addition, 98.0% EA and 93.4% CA were achieved for E. faecalis, with no very major errors (VME) or major errors (ME). According to EUCAST breakpoints for intravenous fosfomycin use, Enterobacterales and Staphylococcus spp. also met ISO acceptance criteria for EA and CA (EA 91.5%, 94.0%, respectively, and CA 98.0% for both). A VME rate of 8.8% was observed for Enterobacterales but the MICs were within EA. A trend to predict lower MICs for Citrobacter spp., E. coli and Salmonella enterica and to predict higher MICs for Klebsiella pneumoniae MICs was observed, while ETEST FO should not be used for Enterobacter cloacae, because of low EA and a high VME rate. The study results support the efficiency of the novel ETEST FO, making it an easy-to-handle tool as a substitute to the classical agar dilution method.

Genetic basis for soma is present in undifferentiated volvocine green algae.

Somatic cellular differentiation plays a critical role in the transition from unicellular to multicellular life, but the evolution of its genetic basis remains poorly understood. By definition, somatic cells do not reproduce to pass on genes and so constitute an extreme form of altruistic behaviour. The volvocine green algae provide an excellent model system to study the evolution of multicellularity and somatic differentiation. In Volvox carteri, somatic cell differentiation is controlled by the regA gene, which is part of a tandem duplication of genes known as the reg cluster. Although previous work found the reg cluster in divergent Volvox species, its origin and distribution in the broader group of volvocine algae has not been known. Here, we show that the reg cluster is present in many species without somatic cells and determine that the genetic basis for soma arose before the phenotype at the origin of the family Volvocaceae approximately 200 million years ago. We hypothesize that the ancestral function was involved in regulating reproduction in response to stress and that this function was later co-opted to produce soma. Determining that the reg cluster was co-opted to control somatic cell development provides insight into how cellular differentiation, and with it greater levels of complexity and individuality, evolves.

Landau-Kleffner syndrome: acquired epileptic aphasia in children.

Acquired epileptic aphasia, or Landau-Kleffner syndrome (LKS), once thought to be a rare syndrome, may occur more frequently in the pediatric population than once thought. This syndrome is typically characterized by an abrupt or gradual loss of language ability and inattentiveness to sound, sometimes called auditory agnosia, with onset during the first 5 years of life. This interruption in communication ability is generally closely preceded, accompanied, or followed by the onset of seizure activity and/or abnormal electro-encephalographic (EEG) findings. This report describes two cases of LKS evaluated at the same hearing and speech center. Because of the characteristic language regression and inattentiveness to sound, speech-language pathologists and audiologists are likely to be among the first professionals to evaluate these children. It is imperative that communication specialists be alert to the characteristic symptoms of LKS in order to be instrumental in initiating an appropriate diagnostic and management process. A multidisciplinary approach to identification and rehabilitation is encouraged in order to effectively re-establish communication skills for these children.

Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain.

The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also activate a wide range of co-transfected promoters without E2P cores to a lower extent. Analysis of multiple E2 mutants in transfected cells revealed that the C-terminal DNA binding E2 domain binds to the E2P cis sequences in the form of pre-existing nuclear dimers. The DNA binding function of E2 was required for specific trans-activation of the E2P elements, as well as for the function of the previously described C-terminal 'short E2' transrepressor. In addition to the C terminus, specific trans-activation also required an intact N-terminal half of the E2 protein. When expressed alone, the N-terminal E2 domain was found to activate heterologous promoters without E2P elements to an extent comparable to wild-type E2, and therefore represents the functional transcription activation domain of the E2 factor. In contrast to other DNA-binding activator proteins described to date, the transcriptional activation by the E2 factor can occur without specific DNA binding. Its mechanism may thus involve protein--protein interactions between common transcription factors and the N-terminal E2 domain which contains amphipathic helix motifs.

Measurement of protein using bicinchoninic acid.

Bicinchoninic acid, sodium salt, is a stable, water-soluble compound capable of forming an intense purple complex with cuprous ion (Cu1+) in an alkaline environment. This reagent forms the basis of an analytical method capable of monitoring cuprous ion produced in the reaction of protein with alkaline Cu2+ (biuret reaction). The color produced from this reaction is stable and increases in a proportional fashion over a broad range of increasing protein concentrations. When compared to the method of Lowry et al., the results reported here demonstrate a greater tolerance of the bicinchoninate reagent toward such commonly encountered interferences as nonionic detergents and simple buffer salts. The stability of the reagent and resulting chromophore also allows for a simplified, one-step analysis and an enhanced flexibility in protocol selection. This new method maintains the high sensitivity and low protein-to-protein variation associated with the Lowry technique.

Long-term passive enhancement of allogeneic skin grafts with monoclonal antibodies.

Monoclonal antibodies (mAb) to graft-specific class I or class II major histocompatibility antigens were tested for their ability to enhance the survival of allogeneic skin transplants. Mutant mouse strains were grafted with wild type tissue to restrict the antigenic differences being recognized. For allogeneic recognition of the class I antigen Ld, mutant BALB/c-H-2dm2 (dm2) mice were grafted with wild type BALB/cKh skin, and two dm2 anti-BALB/cKh mAb, 23-10-1 and 30-5-7, were tested for their ability to enhance. The anti-Ld antibody 23-10-1 (IgM) was found not to enhance the survival of BALB/c skin on dm2 mice. 30-5-7, however, an IgG2a antibody of indistinguishable specificity from 23-10-1, prolonged graft survival for approximately 5 days. For recognition of selected Iab determinants, mutant B6.C-H-2bm12 (bm12) mice were grafted with wild type B6/Kh skin, and mAb specific for the serological change(s) in bm12 were tested for their ability to enhance. The anti-Iab antibody 25-9-17 (IgG2a) was found not to enhance B6 grafts on bm12 mice. However, the enhancement seen with 25-9-17 using (C3H X bm12)F1 recipients was extraordinary, such that treated mice had a mean survival time three times that of the controls. Since 25-9-17 is of C3H origin, these results suggest that allotype (or possibly idiotype) compatibility is important in antibody enhancement. Another anti-Iab antibody 28-16-8 (IgM), also of C3H origin, failed to enhance a B6 graft on (C3H X bm 12)F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)

2-[3-(1,1-Dimethylethyl)-5-methoxyphenyloxazolo[4,5-b]pyridine, a new topical antiinflammatory and analgesic compound lacking systemic activity and gastric side effects.

The substituted oxazolopyridine 2-[3-(1,1-dimethylethyl)-5-methoxyphenyl]oxazolo[4,5-b]pyridine (OZP) inhibits phorbol myristate acetate-induced increases in vascular permeability and neutrophil accumulation in rat ears with ED50 of 253 and 200 micrograms, respectively. This compound is as potent as indomethacin to inhibit UV-induced erythema in guinea pig skin and is an effective analgesic when applied topically to the rat footpad in the yeast hyperalgesia model. OZP is a cyclooxygenase inhibitor with an IC50 of 0.06 mumol/l and inhibits prostaglandin E2, but not leukotriene C4 synthesis, by mouse peritoneal macrophages. This compound is inactive in the carrageenan paw edema assay at 90 mg/kg when administered orally or intraperitoneally, but is effective when injected into the paw. OZP is not a contact allergen and does not cause gastric irritation in rats at doses up to 180 mg/kg orally. OZP is rapidly metabolized by rat liver microsomes in a concentration and time dependent manner. Furthermore, when administered orally, OZP is cleared rapidly in rats with plasma levels being detected only at 5 and 30 min following a 2 mg/kg dose. There was no drug in the gastrointestinal tract of rats 3 h after an oral dose. Thus, this compound appears to be a new, potent and safe topical antiinflammatory and an analgesic agent lacking systemic effects.

Progressive muscle disease in a young woman with family history of Duchenne's muscular dystrophy.

A 16-year-old girl with an extensive family history of Duchenne's muscular dystrophy (DMD) had clinical and laboratory evidence of progressive muscle disease in preadolescence. Other female members of the kindred had exceptionally high creatine phosphokinase levels, and her mother was also symptomatic. Although manifesting carriers of DMD are common, they usually demonstrate a mild and static myopathy. This patient is unusual because her muscle disease was progressive and disabling.

Heart rate changes in convulsive and nonconvulsive neonatal apnea.

One hundred twelve apneic spells of at least 4 seconds' duration were monitored in 15 neonates; 77 episodes were associated with convulsive discharges on the electroencephalogram and 35 were not. Convulsive apnea did not occur in conjunction with bradycardia. Nonconvulsive apnea of less than 20 seconds' duration occurred in the presence of variable heart rates, but nonconvulsive apnea of 20 seconds or longer was nearly always associated with bradycardia.