Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Swiss veterinary health care providers: detection of livestock- and healthcare-associated clones.

We screened a total of 340 veterinarians (including general practitioners, small animal practitioners, large animal practitioners, veterinarians working in different veterinary services or industry), and 29 veterinary assistants for nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP) at the 2012 Swiss veterinary annual meeting. MRSA isolates (n = 14) were detected in 3.8 % (95 % CI 2.1 - 6.3 %) of the participants whereas MRSP was not detected. Large animal practitioners were carriers of livestock-associated MRSA (LA-MRSA) ST398-t011-V (n = 2), ST398-t011-IV (n = 4), and ST398-t034-V (n = 1). On the other hand, participants working with small animals harbored human healthcare-associated MRSA (HCA-MRSA) which belonged to epidemic lineages ST225-t003-II (n = 2), ST225-t014-II (n = 1), ST5-t002-II (n = 2), ST5-t283-IV (n = 1), and ST88-t186-IV (n = 1). HCA-MRSA harbored virulence factors such as enterotoxins, ß-hemolysin converting phage and leukocidins. None of the MRSA isolates carried Panton-Valentine leukocidin (PVL). In addition to the methicillin resistance gene mecA, LA-MRSA ST398 isolates generally contained additional antibiotic resistance genes conferring resistance to tetracycline [tet(M) and tet(K)], trimethoprim [dfrK, dfrG], and the aminoglycosides gentamicin and kanamycin [aac(6')-Ie - aph(2')-Ia]. On the other hand, HCA-MRSA ST5 and ST225 mainly contained genes conferring resistance to the macrolide, lincosamide and streptogramin B antibiotics [erm(A)], to spectinomycin [ant(9)-Ia], amikacin and tobramycin [ant(4')-Ia], and to fluoroquinolones [amino acid substitutions in GrlA (S84L) and GyrA (S80F and S81P)]. MRSA carriage may represent an occupational risk and veterinarians should be aware of possible MRSA colonization and potential for developing infection or for transmitting these strains. Professional exposure to animals should be reported upon hospitalization and before medical intervention to allow for preventive measures. Infection prevention measures are also indicated in veterinary medicine to avoid MRSA transmission between humans and animals, and to limit the spread of MRSA both in the community, and to animal and human hospitals.

The effect of under-treatment of breast cancer in women 80 years of age and older.

BACKGROUND: Several authors have demonstrated a trend toward the under-treatment of elderly and very elderly women with breast cancer. This study was undertaken to determine the impact of under-treatment of breast cancer in women age 80 and older. METHODS: A retrospective chart review of all patients 80 years and older with a newly diagnosed breast cancer at the MD Anderson Cancer Center, Houston, TX, between September 1, 1989 and September 1, 2004 was performed. Data extracted from charts included patient demographics, comorbidity, treatments recommended, treatments received, complications of therapy, disease recurrence and disease related death. Treatments undertaken were analyzed in the context of accepted therapy at the time of diagnosis. RESULTS: Two hundred twelve patients were identified. The median age was 83.5 years (range 80-97). Overall survival in the entire cohort was 7.28 years with a median follow up of 4 years for patients still alive at the end of the study period. Fifty seven percent of patients were under-treated according to institutional and national guidelines. Women who underwent hormonal therapy only demonstrated decreased disease specific survival (P<0.001 respectively) compared with patients who received multi-modality therapy. Women who underwent partial mastectomy without radiation treatment experienced a significant increase in local regional recurrence (P=0.045). There was an association of increased disease specific survival in patients who had surgical lymph node evaluation compared to those who did not (P=0.04). CONCLUSIONS: Outcomes are compromised in very elderly women with breast cancer in whom less than complete combined modality treatment is undertaken. With the previously demonstrated safety of radiation therapy, hormonal therapy and surgery in the very elderly population, multi-modality therapy should not be routinely withheld in patients in this age category.

An in-the-ear platform for recording electroencephalogram.

We introduce a novel approach to brain monitoring based on electroencephalogram (EEG) recordings from within the ear canal. While existing clinical and wearable systems are limited in terms of portability and ease of use, the proposed in-the-ear (ITE) recording platform promises a number of advantages including ease of implementation, minimally intrusive electrodes and enhanced accuracy (fixed electrode positions). It thus facilitates a crucial step towards the design of brain computer interfaces that integrate naturally with daily life. The feasibility of the ITE concept is demonstrated with recordings made from electrodes embedded on an earplug which are benchmarked against conventional scalp electrodes for a classic EEG paradigm.

Sensorimotor reorganization by proprioceptive training in musician's dystonia and writer's cramp.

OBJECTIVE: The sensorimotor organization (SMO) of the motor hand area is abnormal in focal hand dystonia and likely contributes to symptom manifestation. In healthy subjects SMO is changed by training with proprioceptive stimulation. Here we test whether similar interventions reverse the abnormal SMO in musician's dystonia and writer's cramp. If so, they could be developed for therapeutic application. METHODS: In six non-musicians, six professional musicians, six patients with musician's dystonia, and six patients with writer's cramp, SMO was explored by measuring changes in short-interval-intracortical-inhibition (SICI) during short periods of hand muscle vibration before and after two training types: AttVIB, involving attention to 15 minutes vibration of the abductor pollicis brevis (APB); and AttIndex, involving attention to subtle cutaneous stimulation of the index finger. RESULTS: In healthy non-musicians, baseline SMO is spatially differentiated: SICI is reduced in projections to the vibrated, but enhanced to the non-vibrated muscles. Here AttVIB increased and AttIndex reduced the effect of subsequent APB-vibration on SMO. In healthy musicians, baseline SMO is less differentiated. AttVIB reinstated a more differential SMO pattern while AttIndex attenuated the effect of APB vibration. In focal hand dystonia, SMO is completely dedifferentiated. AttVIB tended to restore a more differential SMO in musician's dystonia but not in writer's cramp while AttIndex failed to induce any changes in both groups. CONCLUSION: The intervention effect depends on the pre-interventional sensorimotor organization (SMO). In focal hand dystonia, particularly in musician's dystonia, it is possible to retrain an abnormal SMO toward a more differential pattern, which has potential implications for therapy.

Disturbances of grip force behaviour in focal hand dystonia: evidence for a generalised impairment of sensory-motor integration?

BACKGROUND: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration. OBJECTIVE: To examine how well subjects with writer's cramp (n = 4) or musician's cramp (n = 5) adapted their grip force when lifting a new object or catching a weight. METHODS: Nine patients with focal hand dystonia and 10 controls were studied. Experiments addressed different motor behaviours: (A) lifting and holding an object; (B) adjusting grip force in anticipation of or in reaction to a change in load force by catching a small weight dropped expectedly or unexpectedly into a hand held receptacle. RESULTS: In (A), patients produced a grip force overshoot during the initial lifts; force overflow was most pronounced in those with writer's cramp. Patients and controls adjusted their grip force to object weight within one or two lifts, though patients settled to a steady force level above normal. In (B), patients with focal hand dystonia and normal controls showed similar predictive grip force adjustments to expected changes in object load, suggesting that this aspect of sensory-motor integration was normal. Patients had a shorter latency of grip force response than controls after an unexpected load increase, reflecting either a greater level of preparatory motor activity or a disinhibited spinal reflex response. CONCLUSIONS: The overall increased grip force in patients with focal hand dystonia is likely to be a prelearned phenomenon rather than a primary disorder of sensory-motor integration.

Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human.

Training of a thumb movement in the opposite direction of a twitch in response to transcranial magnetic stimulation (TMS) induces a transient directional change of post-training TMS-evoked movements towards the trained direction. Functional synaptic mechanisms seem to underlie this rapid training-induced plasticity. Transcranial direct current stimulation (tDCS) induces outlasting changes of cerebral excitability, thus presenting as promising tool for neuroplasticity research. We studied the influence of tDCS, applied over the motorcortex during training, on angular deviation of post-training to pre-training TMS-evoked thumb movements. With tDCS of anodal and cathodal polarity the training-induced directional change of thumb movements was significantly reduced during a 10 min post-training interval, indicating an interference of tDCS with mechanisms of rapid training-induced plasticity.

Alteration of sensorimotor integration in musician's cramp: impaired focusing of proprioception.

OBJECTIVE: The influence of muscle vibration (MV) as a strong proprioceptive input on motorcortical excitability was studied in 5 patients with musician's cramp, 5 musician controls and 5 non-musician controls. METHODS: The relaxed flexor carpi radialis (FCR), involved in the dystonic movement in all patients, was vibrated using low frequency (80 Hz) and low amplitude (0.5 mm). Transcranial magnetic stimulation (TMS; intensity, 120% of motor threshold) was applied without MV, 3 and 9 s after the onset of MV. Motor-evoked potentials (MEPs) in the FCR and in the antagonistic extensor carpi radialis (ECR) were recorded. RESULTS: With MV, musician and non-musician controls showed a facilitation of MEPs in the FCR and a decrease of MEPs in the ECR. In musician's cramp, both phenomena were significantly less pronounced. CONCLUSIONS: The reduced facilitation of MEPs in musician's cramp indicates a reduced MV-induced activation of motorcortical areas representing the FCR. The less pronounced inhibition by MV reflects a reduced inhibitory control of the antagonistic ECR. As there were no differences between musician and non-musician controls, the observed changes in musician's cramp refer to this special form of focal dystonia. An impairment of focused motorcortical activation by proprioceptive input from a muscle involved in the dystonic movement is suggested.

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.

Transmission disequilibrium and sequence variants at the leptin receptor gene in extremely obese German children and adolescents.

Genetic determinants of the degree of obesity and body fat distribution have been demonstrated by family studies. The heritability has been estimated to be in the range 0.2-0.7. Mutation leading to obesity in humans has been described for only two genes, one of them the leptin gene. The leptin gene codes for a cytokine secreted by fat cells that binds to the leptin receptor (Lep-R), which exerts some of its biological functions by expression in the brain. Hence, the Lep-R gene appears to be a promising candidate for the determination of obesity in humans. We isolated genomic DNA clones from the Lep-R gene region and identified a new polymorphic microsatellite marker (OBR-CA) within 80 kb of the translation start of Lep-R. We genotyped this and a second, intragenic microsatellite marker (D1S2852) in 130 nuclear families consisting of extremely obese children and adolescents and both parents. Using the most frequent parental allele of both markers, our analysis revealed a significant transmission disequilibrium for the 266-bp allele of D1S2852 (corrected P-value=0.042). No significant result was obtained with the most frequent allele of OBR-CA (corrected P-value=1.0). However, two rare alleles showed transmission disequilibrium and were subsequently used for constructing a haplotype with the 266-bp allele. This haplotype had a transmission rate of 80% (nominal P-value=0.02). In order to identify the underlying mutation, we sequenced all coding exons of Lep-R and the partially overlapping gene encoding the obese receptor gene-related protein (ob-rgrp) in individuals carrying this haplotype. We found one new mutation (Ser675Thr) in the Lep-R gene in one proband and several other mutations known to be not associated with obesity in other study groups. As this new mutation cannot explain our positive linkage result, the transmission disequilibrium of the 266-bp allele and the high transmission rate of the identified haplotype point towards a mutation in close proximity to marker D1S2852.

Systematic mutation screening of the estrogen receptor beta gene in probands of different weight extremes: identification of several genetic variants.

Estrogens are known to have an inhibitory effect on food intake in rodents and primates. Decreased estrogen levels that are found for instance in menopausal woman and in ovarectomized rodents result in body weight gain. Estrogen can act both in the periphery and in the central nervous system via at least two different estrogen receptors (alpha and beta). We systematically screened the coding region and part of the 5' and 3'regions of the estrogen receptor beta gene (ER beta) in 96 extremely obese children and adolescents, 50 patients with anorexia nervosa (AN), 28 patients with bulimia nervosa (BN), and 25 healthy underweight individuals. We detected five different sequence variants in the ER beta: a) A 21 bp deletion (codons 238 to 244) was detected in two obese probands and an underweight individual. b) An 846G-->A transition leading to a nonconservative amino acid substitution (G-250-S) was found in two obese male probands. Both a) and b) were located within the flexible hinge region between DNA and ligand binding domain. c) For a 1082G-->A polymorphism we found suggestive evidence for an association between the more common 1082G-allele and anorexia nervosa (nominal p=0.04). d) One silent mutation (1421T-->C) was found solely in two obese probands. e) A common variant is located in the 3' nontranslated region at position 1730(A-->G). We did not detect association of this polymorphism to any of the analyzed phenotypes. We conclude that the ER beta harbors several different mutations and polymorphisms, none of which can readily be associated with the phenotypes under study.

Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes.

OBJECTIVE: The neuropeptide Y (NPY) Y5 receptor is presumed to be involved in the regulation of food intake. DESIGN: To investigate the possible role of this receptor in weight regulation, the whole coding region of the NPY Y5 receptor gene was screened for mutations using temperature gradient gel electrophoresis (TGGE). Detected mutations were screened in extended cohorts. STUDY COHORTS AND METHODS: Cohorts of 87 extremely obese children and adolescents, 15 underweight subjects and 25 patients with anorexia nervosa (AN) were initially screened by TGGE. Extended samples of these cohorts (160 obese children and adolescents; mean body mass index (BMI) 33.5 +/- 6.4 kg/m2, 128 underweight subjects; mean BMI 18.4 +/- 1.0 kg/m2 and 58 patients with AN; mean BMI 14.6 +/- 1.7 kg/m2) were screened to determine the frequencies of a detected mutation and a detected polymorphism in the NPY Y5 receptor gene. In addition, a previously described polymorphism in the first intron of the NPY Y1 receptor gene was analysed. RESULTS: The coding region of the NPY Y5 receptor gene encompasses one exon. A single mutation, which results in a non-conservative amino acid substitution in the first extracellular domain of the receptor (Glu-4-Ala), and one silent polymorphism (Gly-426-Gly-Gly) at nucleotide position 1278 (G-->A) were detected by TGGE. Both tests for association and linkage to the NPY Y1 and NPY Y5 receptor polymorphisms were negative among all cohorts. The Glu-4-Ala mutation was found only in a single patient with AN and her mother. CONCLUSION: The results do not support a major role of the NPY Y5 receptor gene in the variability of body weight in children and adolescents.

Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.

OBJECTIVE: The missense mutation (64Trp to 64Arg) in the beta 3-adrenergic-receptor has previously been described to confer a genetic predisposition to the development of obesity. DESIGN: To test the hypothesis we evaluated allele frequencies in children, adolescents and young adults who belonged to different weight groups that were delineated with percentiles for the body mass index (BMI; kg/m2). SUBJECTS: 99 underweight probands (BMI < or = 15th percentile). 80 normal weight probands (BMI: 5th-85th percentile). 238 obese children and adolescents (BMI > or = 97th percentile). 84 patients with anorexia nervosa (AN). MEASUREMENTS: The cohorts were screened by polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR-RFLP) analysis. Data were statistically analysed for association. In addition to these case control studies, the transmission disequilibrium test (TDT) was applied to 80 families of obese probands and to 52 families of patients with AN. RESULTS: Both the tests for association and linkage were negative. The Trp64Arg allele frequencies in the three weight groups (obesity: 0.071; normal weight: 0.081; underweight: 0.056) and the AN patients (0.054) were similar. Extremely obese individuals showed no excess of the Trp64Arg allele. No homozygotes for the Trp64Arg allele were detected. CONCLUSION: Heterozygosity for the Trp64Arg allele is not of major importance in regulation of body weight in individuals younger than 35 y. Additionally, the extreme obese subgroup is not enriched for the polymorphism.

Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa.

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Characterization of a family of repetitive sequences that is eliminated late during macronuclear development of the hypotrichous ciliate Stylonychia lemnae.

A repetitive element from the hypotrichous ciliate Stylonychia lemnae was characterized by restriction and hybridization analysis. This repetitive element is present in about 5,000-7,000 copies per haploid genome in the micronucleus and the macronuclear anlagen. Its DNA sequence is very conserved, but the length of the repetitive sequence blocs is variable. In some cases, it is associated with telomeric sequences and macronucleus-homologous sequences. Restriction analysis of genomic micronuclear and macronuclear anlagen DNA and in situ hybridization showed that the repetitive sequences are amplified during the formation of polytene chromosomes. They are localized in many bands of the polytene chromosomes and are eliminated during the degradation of the polytene chromosomes. Possible functions of the repetitive sequences during macronuclear differentiation are discussed.

Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.

Contrast-enhanced transcranial Doppler US with a new transpulmonary echo contrast agent based on saccharide microparticles.

The purpose of this first patient study (phase II) was to evaluate the clinical usefulness of a new echo contrast agent at transcranial Doppler ultrasonography (US). Twenty patients were selected from a group of 242 patients undergoing conventional transcranial Doppler US who had low (n = 18) or absent (n = 2) Doppler signals from the middle cerebral artery (MCA). The extent and duration of Doppler signal increase was measured in 30 MCAs and in 14 basilar arteries following the intravenous injection of a transpulmonary galactose microparticle suspension (SH U 508 A) at three concentrations (200, 300, and 400 mg/mL). Doppler waveform analysis became possible in 93% (28 of 30) of the MCAs following injection. The maximal increase in average Doppler signal intensity (11 dB at 200 mg/mL, 15 dB at 300 mg/mL, and 17 dB at 400 mg/mL) and the increase in average duration of the signal enhancement (163 seconds at 200 mg/mL, 219 seconds at 300 mg/mL, and 240 seconds at 400 mg/mL) depended on contrast agent concentration. Doppler waveform analysis became possible in 79% (11 of 14) of the basilar arteries. The intravenous injection of this new echo contrast agent markedly increases Doppler signal intensity in patients with nondiagnostic results at conventional Doppler US.