Point mutation tRNA(Ser(UCN)) in a child with hearing loss and myoclonus epilepsy

We report on a family with a 12-year-old boy who suffered from a maternally inherited syndrome characterized by a combination of sensorineural hearing loss, myoclonus epilepsy, ataxia, severe psychomotor retardation, short stature, and diabetes mellitus. First, he showed a muscular hypotonia with hearing loss; later, he developed a myoclonus epilepsy, growth failure, and severe psychomotor retardation. At the age of 10 years, he developed diabetes mellitus. After initiation of combined ubiquinone and vitamin C treatment, we observed a progression in psychomotor development. Lactate and pyruvate levels in blood and cerebrospinal fluid were normal. No ragged red fibers or ultrastructural abnormalities were seen in a skeletal muscle biopsy. Biochemical assays of respiratory chain complex activities revealed decreased activity of complexes I and IV. By sequence analysis of mitochondrial DNA encoding transfer ribonucleic acids (RNAs), a homoplasmic T to C substitution at nucleotide position 7512 was found affecting a highly conserved base pair in the tRNA(ser(UCN)) acceptor stem. Asymptomatic family members of the maternal line were heteroplasmic for the mutation in blood samples. Analysis of mitochondrial DNA in patients with hearing loss and myoclonus epilepsy is recommended, even in the absence of laboratory findings. Therapeutically, ubiquinone and antioxidants can be beneficial.

Slow fertilization of stickleback eggs: the result of sexual conflict?

BACKGROUND: The fertilization success in sperm competition in externally fertilizing fish depends on number and quality of sperm. The time delay between sequential ejaculations may further influence the outcome of sperm competition. Such a time interval can load the raffle over fertilization if fertilization takes place very fast. Short fertilization times are generally assumed for externally fertilizing fish such as the three-spined stickleback (Gasterosteus aculeatus). In this pair-spawning fish, territorial males often try to steal fertilizations in nests of neighbouring males. This sneaking behaviour causes sperm competition. Sneakers will only get a share of paternity when eggs are not fertilized immediately after sperm release. Contrary to males, females may be interested in multiple paternity of their clutch of eggs. There thus may be a sexual conflict over the speed of fertilization. RESULTS: In this study we used two different in vitro fertilization experiments to assess how fast eggs are fertilized in sticklebacks. We show that complete fertilization takes more than 5 min which is atypically long for externally fertilizing fishes. CONCLUSION: This result suggests that the time difference does not imply high costs to the second stickleback male to ejaculate. Slow fertilization (and concomitant prolonged longevity of sperm) may be the result of sexual conflict in which females aimed at complete fertilization and/or multiple paternity.

Exhaustion is associated with reduced habituation of free cortisol responses to repeated acute psychosocial stress

We investigated the association between exhaustion and the habituation of free cortisol responses to repeated stress exposure. The study comprised 25 healthy male subjects (38-59 years) who were confronted three times with the Trier Social Stress Test. Mean cortisol responses showed the well-known general habituation effect. A two-way interaction day by exhaustion (p<0.05) indicated that mean cortisol responses vary across stress sessions depending on the extent of exhaustion. Linear regression revealed a negative dose-response relationship between exhaustion and the degree of habituation (p<0.02). We identified 19 individuals showing a response habituation (negative slope) and 6 individuals showing a response sensitization over the three sessions (positive slope) with the latter reporting higher exhaustion scores. It might be hypothesized that impaired habituation to repeated exposure to the same stressor could reflect a state of increased vulnerability for allostatic load. Absence of normal habituation might be one potential mechanism how exhaustion relates to increased disease vulnerability.

Diversity of Mycoplasma hyopneumoniae in pig farms revealed by direct molecular typing of clinical material

Mycoplasma hyopneumoniae is the etiological agent of enzootic pneumonia in swine. Various reports indicate that different strains are circulating in the swine population. We investigated the variety of M. hyopneumoniae strains by a newly developed genetic typing method based on the polyserine repeat motif of the LppS homolog P146. PCR amplification using M. hyopneumoniae specific, conserved primers flanking the region encoding the repeat motif, followed by sequencing and cluster analysis was carried out. The study included strains isolated from different geographic regions as well as lysates from lung swabs from a series of pig farms in Switzerland. High diversity of M. hyopneumoniae was observed but farms being in close geographic or operative contact generally seemed to be affected by the same strains. Moreover, analysis of multiple samples from single pig farms indicated that these harbored the same, farm-specific strain. The results indicate that multiple strains of M. hyopneumoniae are found in the swine population but that specific strains or clones are responsible for local outbreaks. The method presented is a highly reproducible epidemiologic tool allowing direct typing of M. hyopneumoniae from clinical material without prior isolation and cultivation of strains.

Post-mortem forensic neuroimaging: correlation of MSCT and MRI findings with autopsy results

Multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) are increasingly used for forensic purposes. Based on broad experience in clinical neuroimaging, post-mortem MSCT and MRI were performed in 57 forensic cases with the goal to evaluate the radiological methods concerning their usability for forensic head and brain examination. An experienced clinical radiologist evaluated the imaging data. The results were compared to the autopsy findings that served as the gold standard with regard to common forensic neurotrauma findings such as skull fractures, soft tissue lesions of the scalp, various forms of intracranial hemorrhage or signs of increased brain pressure. The sensitivity of the imaging methods ranged from 100% (e.g., heat-induced alterations, intracranial gas) to zero (e.g., mediobasal impression marks as a sign of increased brain pressure, plaques jaunes). The agreement between MRI and CT was 69%. The radiological methods prevalently failed in the detection of lesions smaller than 3mm of size, whereas they were generally satisfactory concerning the evaluation of intracranial hemorrhage. Due to its advanced 2D and 3D post-processing possibilities, CT in particular possessed certain advantages in comparison with autopsy with regard to forensic reconstruction. MRI showed forensically relevant findings not seen during autopsy in several cases. The partly limited sensitivity of imaging that was observed in this retrospective study was based on several factors: besides general technical limitations it became apparent that clinical radiologists require a sound basic forensic background in order to detect specific signs. Focused teaching sessions will be essential to improve the outcome in future examinations. On the other hand, the autopsy protocols should be further standardized to allow an exact comparison of imaging and autopsy data. In consideration of these facts, MRI and CT have the power to play an important role in future forensic neuropathological examination.

Peri-implant inflammation defined by the implant-abutment interface

An implant-abutment interface at the alveolar bone crest is associated with sustained peri-implant inflammation; however, whether magnitude of inflammation is proportionally dependent upon interface position remains unknown. This study compared the distribution and density of inflammatory cells surrounding implants with a supracrestal, crestal, or subcrestal implant-abutment interface. All implants developed a similar pattern of peri-implant inflammation: neutrophilic polymorphonuclear leukocytes (neutrophils) maximally accumulated at or immediately coronal to the interface. However, peri-implant neutrophil accrual increased progressively as the implant-abutment interface depth increased, i.e., subcrestal interfaces promoted a significantly greater maximum density of neutrophils than did supracrestal interfaces (10,512 +/- 691 vs. 2398 +/- 1077 neutrophils/mm(2)). Moreover, inflammatory cell accumulation below the original bone crest was significantly correlated with bone loss. Thus, the implant-abutment interface dictates the intensity and location of peri-implant inflammatory cell accumulation, a potential contributing component in the extent of implant-associated alveolar bone loss.

Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials

OBJECTIVES: The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson ; Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents. METHODS: All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.

Bacterial decontamination of surgical wounds treated with Lavasept

In a prospective randomized controlled double-blind study in 50 acutely injured patients, bacterially contaminated type 2-4 soft tissue wounds were treated with moist dressings of 0.2% Lavasept (fractionated polyhexamethylenbiguanide and macrogolum 4000) solution (n=28) in comparison with Ringer solution (n=22). Standardized swabs were taken on days 0, 2, 8 and 15 and investigated for microorganisms. For a quantitative evaluation, the number of colony forming units (CFU) was determined by a serial dilution technique. The tissue compatibility and anti-inflammatory effect were rated on a scale of 0 (=bad) to 3 (=very good). The most frequently found microorganism was Staphylococcus aureus, which was isolated from 13 wounds. Use of Lavasept led to a faster and significant reduction in microorganisms on the wound surfaces. The number of CFU per wound remained constant or decreased, in contrast to the wounds treated with Ringer solution. This was true for both Gram-positive and Gram-negative bacteria. There was no evidence of impaired wound healing in either group. The anti-inflammatory effect and the tissue compatibility of Lavasept were rated significantly better than that of Ringer solution. It is concluded that Lavasept combines antiseptic action with good tissue compatibility.

Molecular mechanisms of pathogenicity of Mycoplasma mycoides subsp. mycoides SC

Mycoplasma mycoides subsp. mycoides SC, the aetiological agent of contagious bovine pleuropneumonia (CBPP), is considered the most pathogenic of the Mycoplasma species. Its virulence is probably the result of a coordinated action of various components of an antigenically and functionally dynamic surface architecture. The different virulence attributes allow the pathogen to evade the host's immune defence, adhere tightly to the host cell surface, persist and disseminate in the host causing mycoplasmaemia, efficiently import energetically valuable nutrients present in the environment, and release and simultaneously translocate toxic metabolic pathway products to the host cell where they cause cytotoxic effects that are known to induce inflammatory processes and disease. This strategy enables the mycoplasma to exploit the minimal genetic information in its small genome, not only to fulfil the basic functions for its replication but also to damage host cells in intimate proximity thereby acquiring the necessary bio-molecules, such as amino acids and nucleic acid precursors, for its own biosynthesis and survival.

Validation and diagnostic efficacy of a TaqMan real-time PCR for the detection of Mycoplasma conjunctivae in the eyes of infected Caprinae

Infectious keratoconjunctivitis (IKC), caused by Mycoplasma conjunctivae, is a highly contagious ocular disease in Caprinae. To detect rapidly and sensitively M. conjunctivae from individual conjunctival swabs of infected domestic and wild animals, a specific real-time PCR was developed using an lppS-directed hydrolysis probe in a TaqMan platform.

Beta-D-glucoside utilization by Mycoplasma mycoides subsp. mycoides SC: possible involvement in the control of cytotoxicity towards bovine lung cells

BACKGROUND: Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides small-colony type (SC) is among the most serious threats for livestock producers in Africa. Glycerol metabolism-associated H2O2 production seems to play a crucial role in virulence of this mycoplasma. A wide number of attenuated strains of M. mycoides subsp. mycoides SC are currently used in Africa as live vaccines. Glycerol metabolism is not affected in these vaccine strains and therefore it does not seem to be the determinant of their attenuation. A non-synonymous single nucleotide polymorphism (SNP) in the bgl gene coding for the 6-phospho-beta-glucosidase (Bgl) has been described recently. The SNP differentiates virulent African strains isolated from outbreaks with severe CBPP, which express the Bgl isoform Val204, from strains to be considered less virulent isolated from CBPP outbreaks with low mortality and vaccine strains, which express the Bgl isoform Ala204. RESULTS: Strains of M. mycoides subsp. mycoides SC considered virulent and possessing the Bgl isoform Val204, but not strains with the Bgl isoform Ala204, do trigger elevated levels of damage to embryonic bovine lung (EBL) cells upon incubation with the disaccharides (i.e., beta-D-glucosides) sucrose and lactose. However, strains expressing the Bgl isoform Val204 show a lower hydrolysing activity on the chromogenic substrate p-nitrophenyl-beta-D-glucopyranoside (pNPbG) when compared to strains that possess the Bgl isoform Ala204. Defective activity of Bgl in M. mycoides subsp. mycoides SC does not lead to H2O2 production. Rather, the viability during addition of beta-D-glucosides in medium-free buffers is higher for strains harbouring the Bgl isoform Val204 than for those with the isoform Ala204. CONCLUSION: Our results indicate that the studied SNP in the bgl gene is one possible cause of the difference in bacterial virulence among strains of M. mycoides subsp. mycoides SC. Bgl does not act as a direct virulence factor, but strains possessing the Bgl isoform Val204 with low hydrolysing activity are more prone to survive in environments that contain high levels of beta-D-glucosides, thus contributing in some extent to mycoplasmaemia.