Early and widespread engagement of the cerebellum during hippocampal epileptiform activity Format: Brief Communication.

Despite research illustrating the cerebellum may be a critical circuit element in the epilepsies, remarkably little is known about cerebellar engagement during seizures. We therefore implemented a novel method for repeated imaging of the cerebellum in awake, chronically epileptic animals. We found widespread changes in cerebellar calcium signals during behavioral seizures and during hippocampal seizures that remained electrographic only, arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Changes were noted in the anterior and posterior cerebellum, along the midline, and both ipsilaterally and contralaterally to the seizure focus. Remarkably, changes in the cerebellum also occurred prior to any noticeable change in the hippocampal electrographic recordings, suggesting a special relationship between the cerebellum and hippocampal epileptiform activity. Together these results underscore the importance of the cerebellum in epilepsy, warranting a more consistent consideration of the cerebellum when evaluating epilepsy patients.

Estimation of compliance with exclusive smoking of very low nicotine content cigarettes using plasma cotinine.

Regulations requiring a reduction of the nicotine content in cigarettes to minimally addictive levels could significantly reduce the public health impact of cigarette smoking. Clinical trials evaluating this strategy are ongoing and methods have been developed to use nicotine biomarkers to estimate compliance with use of very low nicotine content cigarettes (VLNCs). To date, these methods have not considered the potential contribution of nicotine absorption from environmental tobacco smoke (ETS) among research participants. This study used data from 100 randomly selected study completers in ongoing clinical trials of VLNCs (50 randomized to Usual Nicotine Content Cigarettes (UNCs) and 50 to VLNCs) to assess the use of plasma cotinine to estimate compliance. Plasma cotinine and smoking behavior were recorded at baseline after 2 weeks smoking UNC cigarettes, and then after 18 weeks of either continuing smoking UNCs or reducing the nicotine content such that the last 6 weeks comprised smoking VLNCs. Plasma cotinine remained stable (267 ng/ml) in the UNC group but reduced to 93 ng/ml in the VLNC group (p < 0.01). Compliance with smoking VLNCs was first estimated by comparing the cotinine per cigarette on VLNCs with UNCs after allowing for potential compensatory smoking. We found that 29 (58%) of the VLNC group were compliant. Adjusting for potential ETS exposure estimated 32 (64%) to be compliant. This latter group (n = 32) had a mean plasma cotinine on VLNCs of 7 ng/ml (range = 3-16.4 ng/ml). Adjusting for potential ETS exposure may improve identification of participants who plausibly complied with exclusive VLNC use.

[Psychological assessment of visual hemispatial neglect: standardization and approbation of the modified digit cancellation test]. / Diagnostika odnostoronnego zritel'no-prostranstvennogo nevnimaniia: standartizatsiia i aprobatsiia modifitsirovannoi tsifrovoi korrekturnoi proby.

AIM: To study the phenomena of visual-hemispatial neglect in healthy people and patients with brain diseases of different genesis. MATERIAL AND METHODS: Eighty-eight patients with schizophrenia spectrum disorders, 68 patients with exogenous organic brain diseases and 240 healthy adults of different age were included in the study. The digit cancellation test modified by the authors was used. RESULTS AND CONCLUSION: The validity of the modified digit cancellation test was approved and its age standards were obtained. In healthy right-handed people, there was the bias of attention focus to the left, the decrease of asymmetry intensity of visual-spatial inattention during physiological aging and the presence of some clinical peculiarities of neglect in schizophrenia spectrum disorders and lateralized organic damages of the brain. This variant of the test can be recommended for practical use as the sensitive psychometric tool.

Illuminating the conceptual structure of the space of moral violations with searchlight representational similarity analysis.

Characterizing how representations of moral violations are organized, cognitively and neurally, is central to understanding how people conceive and judge them. Past work has identified brain regions that represent morally relevant features and distinguish moral domains, but has not yet advanced a broader account of where and on what basis neural representations of moral violations are organized. With searchlight representational similarity analysis, we investigate where category membership drives similarity in neural patterns during moral judgment of violations from two key moral domains: Harm and Purity. Representations converge across domains in a network of regions resembling the mentalizing network. However, Harm and Purity violation representations respectively converge in different regions: precuneus (PC) and left inferior frontal gyrus (LIFG). Examining substructure within moral domains, Harm violations converge in PC regardless of subdomain (physical harms, psychological harms), while Purity subdomains (pathogen-related violations, sex-related violations) converge in distinct sets of regions - mirroring a dissociation observed in principal-component analysis of behavioral data. Further, we find initial evidence for representation of morally relevant features within these two domain-encoding regions. The present analyses offer a case study for understanding how organization within the complex conceptual space of moral violations is reflected in the organization of neural patterns across the cortex.

Selective attention and pigeons' multiple necessary cues discrimination learning.

We deployed the Multiple Necessary Cues (MNC) discrimination task to see if pigeons can simultaneously attend to four different dimensions of complex visual stimuli. Specifically, we trained eight pigeons on a simultaneous discrimination to peck only 1 of 16 compound stimuli created from all possible combinations of two stimulus values from four separable visual dimensions: shape (circle/square), size (large/small), line orientation (horizontal/vertical), and brightness (dark/light). Some pigeons had CLHD (circle, large, horizontal, dark) as the positive stimulus (S+), whereas others had SSVL (square, small, vertical, light) as the S+. All eight pigeons acquired the MNC discrimination, suggesting that they had attended to all four dimensions. Learning rate was similar to all four dimensions, with learning along the orientation dimension being a bit faster than along the other three dimensions. The more dimensions along which the S-s differed from the S+, the faster was learning, suggesting an added benefit from increasing perceptual disparities between the S-s and the S+. Of particular note, evidence of attentional tradeoffs among the four dimensions was much weaker with the simultaneous task than with the successive task. We consider several reasons for this empirical disparity.

In vitro characterization of representative clinical South African Staphylococcus aureus isolates from various clonal lineages.

Data concerning the virulence and pathogenesis of South African strains of Staphylococcus aureus are limited. We investigated host-pathogen interactions of randomly selected clinical S. aureus isolates representing various clones. We characterized the ability of isolates to adhere to fibronectin, fibrinogen, collagens IV and VI, to invade host cells and to induce cell death in vitro. We analysed the possible association of these results with characteristics such as methicillin resistance, Panton-Valentine leucocidin (PVL) positivity and clonality. The S. aureus isolates displayed diversity in their abilities to adhere to various human ligands. All isolates were highly invasive except for ST121. PVL-negative isolates were significantly more invasive than the PVL-positive isolates (p 0.004). Isolates of CC5, CC30 and CC121 were non-cytotoxic, whereas isolates of CC22, CC8, CC15, CC45 and CC88 were very cytotoxic. No statistical association was identified between cell death and methicillin resistance, bacterial PVL status, clonality or patient HIV status. The vast majority of isolates were invasive and induced significant cell death. PVL-negative isolates were more invasive than PVL-positive isolates, while methicillin-resistant isolates were not found to be more invasive or cytotoxic than methicillin-susceptible isolates.

Attentional tradeoffs in the pigeon.

We deployed the Multiple Necessary Cues (MNC) discrimination task to see if pigeons can simultaneously attend to four different dimensions of complex visual stimuli. Specifically, we trained nine pigeons (Columba livia) on a go/no go discrimination to peck only 1 of 16 compound stimuli created from all possible combinations of two stimulus values from four separable visual dimensions: shape (circle/square), size (large/small), line orientation (horizontal/vertical), and brightness (dark/light). Some of the pigeons had CLHD (circle, large, horizontal, dark) as the positive stimulus (S+), whereas others had SSVL (square, small, vertical, light) as the S+. We recorded touchscreen pecking during the first 15 s that each stimulus was presented on each training trial. Discrimination training continued until pigeons' rates of responding to all 15 negative stimuli (S-s) fell to less than 15% of their response rates to the S+. All pigeons acquired the MNC discrimination, suggesting that they attended to all four dimensions of the multidimensional stimuli. Learning rate was similar for all four dimensions, indicating equivalent salience of the discriminative stimuli. The more dimensions along which the S-s differed from the S+, the faster was discrimination learning, suggesting an added benefit from increasing perceptual disparities of the S-s from the S+. Finally, evidence of attentional tradeoffs among the four dimensions was seen during discrimination learning, raising interesting questions concerning the possible control of behavior by elemental and configural stimuli.

Population structure analyses of Staphylococcus aureus at Tygerberg Hospital, South Africa, reveals a diverse population, a high prevalence of Panton-Valentine leukocidin genes, and unique local methicillin-resistant S. aureus clones.

Studies reporting on the population structure of Staphylococcus aureus in South Africa have focused only on methicillin-resistant S. aureus (MRSA). This study describes the population structure of S. aureus, including methicillin-susceptible S. aureus (MSSA) isolated from patients at Tygerberg Academic Hospital, Western Cape province. Pulsed-field gel electrophoresis (PFGE), detection of Panton-Valentine leukocidin (PVL), spa typing, multilocus sequence typing (MLST), agr typing and SCCmec typing were used to characterize strains. Of 367 non-repetitive S. aureus isolates collected over a period of 1 year, 56 (15.3%) were MRSA. Skin and soft tissue infections were the most frequent source (54.8%), followed by bone and joint (15.3%) and respiratory tract infections (7.7%). For strain typing, PFGE was the most discriminative method, and resulted in 31 pulsotypes (n = 345, 94.0%), as compared with 16 spa clonal complexes (CCs) (n = 344, 93.4%). Four MLST CCs were identified after eBURST of sequence types (STs) of selected isolates. One hundred and sixty isolates (MSSA, n = 155, 42.2%) were PVL-positive, and agr types I-IV and SCCmec types I-V were identified. Our S. aureus population consisted of genotypically diverse strains, with PVL being a common characteristic of MSSA. MSSA and MRSA isolates clustered in different clones. However, the dominant MRSA clone (ST612) also contained an MSSA isolate, and had a unique genotype. Common global epidemic MRSA clones, such as ST239-MRSA-III and ST36-MRSA-II, were identified. A local clone, ST612-MRSA-IV, was found to be the dominant MRSA clone.

Superior Detection of Pathogens in Synovial Fluid by the Bactec 9240 Peds Plus/F System Compared to the Conventional Agar-based Culture Method

To improve culture yield in cases of possible septic arthritis; we compared culture of joint fluid aspirates on conventional agar-based media to culture in Bactec 9240 Peds/Plus F blood culture bottles with and without the addition of fastidious organism supplement (FOS). Over a period of 21 months; we analysed 123 synovial fluid samples and isolated 20 pathogens. The Bactec methods proved superior by yielding more pathogens than the conventional culture method (p=0.074). However; this method also yielded more contaminants within the first three days of incubation (p=0.027). All contaminants detected after three days of incubation were the result of overgrowth on conventional method agar plates. The Bactec methods provided clinicians with a positive pathogen result one day earlier than the conventional counterpart (p=0.001). Four isolates of Neisseria gonorrhoeae were only cultured with the Bactec method. No significant benefit was demonstrated by supplementing blood culture bottles with FOS. We recommend that whenever infection by fastidious organisms is suspected; synovial fluid aspirates should be cultured using automated blood culture systems to increase the culture yield and to decrease the time to detection

Improvement in mycobacterial yield and reduced time to detection in pediatric samples by use of a nutrient broth growth supplement.

There is an urgent need to improve the methods used for the bacteriological diagnosis of childhood mycobacterial disease. This study compared the mycobacterial yields and the times to detection (in days) of mycobacteria in pediatric clinical specimens by using Mycobacterial Growth Indicator Tubes (MGITs) and solid Löwenstein-Jensen (LJ) slants with and without a nutrient broth supplement. A total of 801 specimens from 493 patients were processed: 82.8% were gastric aspirate specimens, 15.6% were sputum specimens, and 1.6% were fine-needle-aspiration biopsy specimens. The mycobacterial yield obtained with MGITs (with and without nutrient broth) was 11.0%, and that obtained with LJ slants was 1.6% (P < 0.001). Of the 88 positive cultures, 62 were detected in MGITs and 73 were detected in MGITs supplemented with nutrient broth (P = 0.11). The mean time to detection in MGITs (without nutrient broth) was 18.5 days, whereas it was 12.4 days in MGITs with nutrient broth (P < 0.001). Supplementation of standard MGITs improved the mycobacterial yield and significantly reduced the time to detection of mycobacteria in pediatric samples.

Antimicrobial Susceptibility Patterns of Selected Invasive Pathogens from Public Sector Hospitals in South Africa; 2007

Retrospective antibiotic surveillance data of selected invasive pathogens isolated from blood and cerebrospinal fluid at public sector hospitals in South Africa in 2007 are presented. Antimicrobial susceptibilities were determined according to the 2007 Clinical and Laboratory Standards Institute criteria. Klebsiella pneumoniae remains a highly resistant pathogen; with approximately half of all strains producing extended-spectrum beta-lactamases. All laboratories reported considerable resistance among Acinetobacter spp. Approximately 50-60of Staphylococcus aureus isolates from blood were resistant to cloxacillin. Among Streptococcus pneumoniae isolates from blood and cerebrospinal intermediate resistance to penicillin. Resistance to ceftriaxone in S. pneumoniae was rare

Escalation in the relative prevalence of ciprofloxacin-resistant gonorrhoea among men with urethral discharge in two South African cities: association with HIV seropositivity.

OBJECTIVES: The objectives of this study were to assess the prevalence of ciprofloxacin-resistant gonorrhoea in two South African cities and to investigate the association between the isolation of ciprofloxacin-resistant Neisseria gonorrhoeae and the HIV serostatus of patients. METHODS: Gonococci were cultured from endourethral swabs taken from consecutive men with urethritis attending clinics in Johannesburg and Cape Town. Minimum inhibitory concentrations (MIC) for ciprofloxacin and ceftriaxone were determined with E-tests. Isolates with a ciprofloxacin MIC of 1 mg/l or greater were defined as resistant and isolates with a ceftriaxone MIC of 0.25 mg/l or less were defined as susceptible. Rapid tests were used to screen and confirm the presence of HIV antibodies. Survey data from 2004 were used as a baseline to assess trends in gonococcal resistance to ciprofloxacin. RESULTS: In 2004, the prevalence of ciprofloxacin resistance was 7% in Cape Town and 11% in Johannesburg. In 2007, 37/139 (27%) Cape Town isolates and 47/149 (32%) Johannesburg isolates were resistant to ciprofloxacin; in comparison with 2004 data, this represents 2.9-fold and 1.9-fold increases, respectively. All isolates were fully susceptible to ceftriaxone. There was a significant association between HIV seropositivity and the presence of ciprofloxacin-resistant gonorrhoea among patients (p = 0.034). CONCLUSIONS: Johannesburg and Cape Town have witnessed significant rises in the prevalence of ciprofloxacin-resistant gonorrhoea among men with urethritis. The resistant phenotype is linked to HIV seropositivity. There is now an urgent need to change national first-line therapy for presumptive gonococcal infections within South Africa.

Clinical rotation in pathology: description of a case based approach.

BACKGROUND: The implementation of a system based, integrated curriculum at the Faculty of Health Sciences of Stellenbosch University, Western Cape, South Africa, resulted in less contact time for the pathology disciplines during theoretical modules, while a weekly rotation in pathology was introduced during clinical training in the fourth and fifth years. OBJECTIVE: To describe a problem based approach for this rotation. METHODS: Students are presented with a clinical "paper" case daily, integrating as many of the pathology disciplines as possible to demonstrate the interdependence of the various disciplines. They receive chemical pathology tutorials, visit the various laboratories, and receive practical training in fine needle aspiration biopsy. On the final day, the case studies are assessed and discussed. RESULTS: Most students appreciated all activities. This rotation enhanced student interactivity and autonomy and guaranteed immediate feedback. On evaluation of the rotation it was found that the students enjoyed the rotation, learnt something new, and realised the value of group work. CONCLUSIONS: This innovation integrates pathology with clinical practice and illustrates the use of laboratory medicine in the management of common diseases seen in this country. Students appreciate learning practical skills and having to request special investigations under a pathologist's supervision changes their approach to pathology requests. Familiarity with the pathology environment empowers the student to use pathology with greater ease. A bank of case studies that can be expanded to include all medical disciplines will facilitate the application of a problem based approach and enhance communication between the basic science disciplines and the clinical and pathology disciplines.

Regular developmental changes in EEG multifractal characteristics.

Electroencephalograms (EEGs) of 110 pupils (aged 6.5-19.5 years; 48 healthy subjects, 51 with cerebral palsy, 11 with acquired cerebral defect) were acquired. The stable age dependences of averaged parameters of k x f-beta EEG spectra model, deviations from the model, and normalized ranges of detrended EEGs were found. These dependences were observed in both healthy subjects and patients, in males and females, in the cases of congenital and acquired pathology. This regularity reflects the process of cerebral maturation and developmental change of structure types of the EEG process, and it is inherent to normal as well as to abnormal brain development.

Toward a theory of variability discrimination: finding differences.

We sketch the outlines of a theory of variability discrimination that aggregates localized differences to mediate variability discrimination. This Finding Differences Model was compared to a Positional Entropy Model across four different data sets. Although the two models provide strong and similar fits across three of the data sets, only the Finding Differences Model is applicable to investigations involving multidimensional variability. Furthermore, the Finding Differences Model is based on an activation map that has been shown to have utility for visual search tasks, thus establishing its generality across task domains.

The chemotherapy of metastatic gastric adenocarcinomas with hypersecretion of alpha-fetoprotein or beta-human chorionic gonadotrophin: report of two cases.

The chemotherapy of advanced gastric adenocarcinomas (GAs) is based on agents such as cisplatin, 5-fluorouracil and anthracyclins. Reproducible objective response rates are reported as approximately 40%. However, the median survival remains short, not exceeding 10 months. Amongst GA, a subset of tumours with increased plasma alpha-fetoprotein (alphaFP) and/or beta human chorionic gonadotrophin (betaHCG) levels form a well-defined histopathological entity. This subgroup has been associated with poor prognosis, due to the presence of poorly differentiated and rapidly proliferating cells. No specific chemotherapy has been proposed for this particular form of GA. We report two cases of patients with GA and hypersecretion of alphaFP and/or betaHCG. Despite bulky liver metastases and resistance to two standard chemotherapy regimens, both patients exhibited sensitivity to chemotherapy combining bleomycin, oxaliplatin and etoposide. These results suggest that patients with this particular subset of GA may benefit from chemotherapy regimens similar to those given to germ-cell tumour patients.

Lack of adverse cognitive effects of 1 Hz and 20 Hz repetitive transcranial magnetic stimulation at 100% of motor threshold over left prefrontal cortex in depression.

OBJECTIVE: The potential therapeutic effects of repetative transcranial magnetic stimulation (rTMS) are being examined in various neuropsychiatric illnesses. This study assesses the cognitive performance of depressed patients receiving high or low frequency rTMS for 10 days. METHODS: 18 depressed patients participated in a randomized double-blind cross-over study exploring the antidepressant effects of 2 weeks (10 daily) of sham, 1 Hz, or 20 Hz rTMS administered over the left dorsolateral prefrontal cortex at 100% of motor threshold (MT). A subgroup completed a battery of cognitive tests at baseline and following each 2-week phase of treatment, and differences in performance were assessed using paired t -tests and were correlated with the degree of clinical improvement using Hamilton Depression Rating Scale scores. RESULTS: There were no major changes in cognitive test scores as a result of 10 days of either 1 Hz or 20 Hz rTMS. Moreover, any minor attenuations in cognition were not related to the degree of clinical improvement. CONCLUSIONS: Cognitive functioning in many domains following 2 weeks of 1 Hz or 20 Hz rTMS at 100% MT over the left dorsolateral prefrontal cortex in depressed patients is not disrupted.

Discriminating the relation between relations: the role of entropy in abstract conceptualization by baboons (Papio papio) and humans (Homo sapiens).

Two baboons (Papio papio) successfully learned relational matching-to-sample: They picked the choice display that involved the same relation among 16 pictures (same or different) as the sample display, although the sample display shared no pictures with the choice displays. The baboons generalized relational matching behavior to sample displays created from novel pictures. Further experiments varying the number of sample pictures and the mixture of same and different sample pictures suggested that entropy plays a key role in the baboons' conceptual behavior. Two humans (Homo sapiens) were similarly trained and tested; their behavior was both similar to and different from the baboons' behavior. The results suggest that animals other than humans and chimpanzees can discriminate the relation between relations. They further suggest that entropy detection may underlie same-different conceptualization, but that additional processes may participate in human conceptualization.