VERTEBRAL OSTEOMYELITIS IN QATAR

SUMMARY Twenty-eight cases of vertebral osteomyelitis were diagnosed at Hamad General Hospital in Qatar between January 1988 and December 1991:16 (57.2%) cases were tuberculous spondylitis, 6 (21.4%) Brucella spondylitis, 3 (10.7%) Staphylococcus aureus spondylitis, 2 (7.1%) Salmonella spondylitis, and 1 (3.6%) Pseudomonas cepacia spondylitis. Plain vertebral x-ray films and CT scans were abnormal in all patients. Bone and gallium scans were abnormal in 87.5% and 64% of cases respectively. Clinical manifestations, haematological and radiological investigations were not able to differentiate between the causes. Serological tests were helpful in diagnosing Brucella spondylitis. CT-guided needle biopsy was able to identify the aetiology in 90% of cases. We conclude that invasive tests are still needed to establish the microbiological diagnosis and to guide antimicrobial therapy in most cases of vertebral osteomyelitis.     

SUBCUTANEOUS ALVEOLAR SOFT-PART SARCOMA MIMICKING METASTATIC HYPERNEPHROMA

SUMMARY Alveolar soft-part sarcoma represents a rare tumour of the subcutaneous and soft tissues that may present to the dermatologist. It may mimic both other primary tumours and other metastatic tumours. This mimickry has not been emphasised in the previous literature.     

Gut microbial markers are associated with diabetes onset,regulatory imbalance,and IFN-γ level in NOD Mice

Gut microbiota regulated imbalances in the host''s immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3⁺ regulatory T cells, CD11b⁺ dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24–7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.     

Ongoing dynamics in large-scale functional connectivity predict perception

Most brain activity occurs in an ongoing manner not directly locked to external events or stimuli. Regional ongoing activity fluctuates in unison with some brain regions but not others, and the degree of long-range coupling is called functional connectivity, often measured with correlation. Strength and spatial distributions of functional connectivity dynamically change in an ongoing manner over seconds to minutes, even when the external environment is held constant. Direct evidence for any behavioral relevance of these continuous large-scale dynamics has been limited. Here, we investigated whether ongoing changes in baseline functional connectivity correlate with perception. In a continuous auditory detection task, participants perceived the target sound in roughly one-half of the trials. Very long (22–40 s) interstimulus intervals permitted investigation of baseline connectivity unaffected by preceding evoked responses. Using multivariate classification, we observed that functional connectivity before the target predicted whether it was heard or missed. Using graph theoretical measures, we characterized the difference in functional connectivity between states that lead to hits vs. misses. Before misses compared with hits and task-free rest, connectivity showed reduced modularity, a measure of integrity of modular network structure. This effect was strongest in the default mode and visual networks and caused by both reduced within-network connectivity and enhanced across-network connections before misses. The relation of behavior to prestimulus connectivity was dissociable from that of prestimulus activity amplitudes. In conclusion, moment to moment dynamic changes in baseline functional connectivity may shape subsequent behavioral performance. A highly modular network structure seems beneficial to perceptual efficiency.The brain is highly active in a continuous manner, and much of neural activity is not directly locked to external events or stimuli. This continuous brain activity is spatiotemporally organized into a functional connectivity architecture that comprises several large-scale networks. Large-scale networks span different cerebral lobes and include subcortical structures (1). The regions comprised in such networks commonly coactivate together in response to task demands (2), but they also show correlated and spontaneous activity fluctuations when no changes occur in the external environment. The functional connectivity architecture ensuing from these activity cofluctuations largely persists across all mental states, including various tasks, resting wakefulness, and sleep, albeit showing some degree of modulation across these states (3, 4).Strength and spatial distributions of functional connectivity within this architecture are not, however, stationary across time. At the spatial level of large-scale networks, functional connectivity shows prominent changes over the range of seconds to minutes (5). These so-called infraslow timescales and the spatial distribution of large-scale networks can be particularly well-investigated using functional MRI (fMRI). We refer to the nonstationarity of functional connectivity as ongoing dynamics. The notion of ongoing refers to dynamics that are not brought about by particular external events, such as stimuli or cues. Such large-scale ongoing network dynamics are thought to be crucial for the brain to explore a large space of dynamic functional capabilities (6). This potential functional importance has recently sparked interest in ongoing connectivity dynamics (5). The most common approach to studying ongoing dynamics in connectivity with fMRI has been to measure connectivity in time windows sliding through a prolonged task-free resting state (reviewed in ref. 5). These investigations have established the nonstationarity of large-scale functional connectivity that previously had been largely neglected. Some studies have shown characteristic changes of dynamic connectivity in different patient populations (7). However, none of these resting-state studies have directly investigated the functional consequences of ongoing dynamics during performance (in other words, how moment to moment changes in baseline functional connectivity relate to cognition and behavior). Furthermore, the ongoing dynamics of functional connectivity may be modulated by cognitive task context, further motivating investigation of the behavioral importance during task beyond the resting state.Several lines of research call for a dedicated investigation of this question. Slow ongoing fluctuations in regional prestimulus baseline activity amplitudes (in fMRI or electrophysiological recordings) in task-relevant sensory or motor regions (8–12) as well as entire large-scale brain networks (12–14) correlate with evoked neural response strength and subsequent behavior. It is not clear whether, beyond fluctuations in regional ongoing activity amplitude, the correlation of such amplitude fluctuations across large-scale network regions (i.e., connectivity) relates to behavioral variability. Some prior work seems to suggest that ongoing connectivity dynamics between two task-relevant regions may turn behaviorally relevant (15). Also, in addition to these effects in infraslow timescales, some electrophysiological recordings indicate a behavioral relevance for phase synchrony between individual regions of interest and the rest of the brain at faster timescales (16). Building on this so-far rather sparse evidence, we here sought to investigate behavioral effects from ongoing dynamics in large-scale functional connectivity, calling on tools of multivariate classification for trial by trial prediction of behavior and graph theory for a more detailed and spatially comprehensive characterization.We analyzed behavioral outcome on a trial by trial basis as a function of dynamic connectivity states before stimulus presentation. We tested whether large-scale functional connectivity states predict perception of a sparse and irregularly appearing stimulus. To investigate ongoing nontask-locked changes in baseline connectivity, we minimized contributions from stimulus-evoked activity. This study, therefore, extends beyond important previous investigations of connectivity dynamics that occur after changes in the external environment (such as stimulation, cues, instructions, or feedback) at infraslow (17–20) and fast electrophysiological timescales (21, 22). Specifically, we asked (i) whether ongoing dynamics of large-scale functional connectivity relate to perceptual performance and (ii) which properties of baseline functional connectivity distinguish brain states that support perceptual accuracy from those that do not.Eleven blindfolded participants performed a detection task on an auditory broadband stimulus (500 ms). They pressed a button whenever they heard the sound during two to three 20-min-long fMRI runs. The stimulus was presented at the individually determined detection threshold and repeated very sparsely at highly variable interstimulus intervals ranging from 20 to 40 s (Fig. 1A). This dataset has previously been used to investigate behavioral correlates of baseline activity amplitudes and enables this investigation to directly compare effects from prestimulus activity amplitudes with those from prestimulus connectivity (12). The unusually long interstimulus interval design allowed us to focus all analyses on the prestimulus time after excluding the hemodynamic response evoked by the previous stimulus. To answer our first question of whether prestimulus baseline connectivity predicts behavior, we applied trial by trial classification of subsequent perceptual outcome based on patterns of functional connectivity before stimulus presentation. To address our second question and determine what characterizes the difference across these brain states, we modeled connectivity before hits and before misses as separate graphs using tools of complex network theory and compared graph metrics between these states.Open in a separate windowFig. 1.(A) Experimental design of a threshold-level auditory stimulus presented on top of background scanner noise at very long, unpredictable interstimulus intervals (ISI, 20–40 s). Participants listened for the faint target sound continuously throughout 20-min runs and pressed a response button whenever they perceived the target. (B) Illustration of baseline time segments unaffected by evoked responses that were defined as appropriate for analysis of ongoing functional connectivity (marked in gray). The illustrated blood-oxygen-level-dependent (BOLD) hemodynamic response peaks at 6 s, reaches maximum poststimulus undershoot at 12 s, and returns to baseline before 16 s relative to stimulus onset according to finite impulse response estimation of the brain response to this stimulus in the same data in 10 bilateral brain areas (12). Baseline segments started after 16 s poststimulus and ended 1 s after the next stimulus onset. Baseline segments shorter than 6 s in length (interstimulus interval <22 s) were excluded. For classification analyses requiring trial by trial data, data were further restricted to baseline segments that were at least 15 s long (10 image volumes and interstimulus intervals ≥31 s). In this exemplary 2-min period of the task, four stimuli (marked as solid vertical lines) occur at interstimulus intervals of 40 (maximum in this design), 20 (minimum), and 32 s. Note that, for simplification, this illustration does not depict the spontaneous signal fluctuations during the baseline period and the ensuing variability in stimulus-evoked hemodynamic responses that are at the heart of this study.     

Platelet secretion defect associated with impaired liberation of arachidonic acid and normal myosin light chain phosphorylation

We describe four patients with impaired platelet aggregation and 14C- serotonin secretion during stimulation with adenosine diphosphate (ADP), epinephrine, collagen, and platelet-activating factor. The response to arachidonic acid was normal in all patients with regard to aggregation and in three of the four with regard to 14C-serotonin secretion. The total platelet adenosine triphosphate (ATP) and ADP content and the ATP to ADP ratio was normal in all patients, thereby excluding storage pool deficiency as the cause of the secretion defect. Studies with 3H-arachidonic acid-labeled platelets revealed that the thrombin-induced liberation of arachidonic acid from membrane-bound phospholipids was impaired in these patients. Further, platelet thromboxane B2 production, measured using a radioimmunoassay, was diminished during stimulation with ADP and thrombin, but was normal with arachidonic acid, indicating that the oxygenation of arachidonic acid was normal and that the diminished thromboxane production was due to a defect in the liberation of arachidonic acid. Release of arachidonic acid is mediated by phospholipases that are Ca++ dependent. To examine whether these patients may have a defect in making intracellular Ca++ available, another Ca++-dependent process, myosin light chain phosphorylation, was studied during thrombin stimulation. Platelets from three of the patients were found to behave the same as normal ones, suggesting that the deficiency in phospholipase activity may not be due to impaired Ca++ mobilization. Our studies demonstrate a novel group of patients with platelet secretion defects associated with impaired liberation of arachidonic acid from phospholipids. These patients exemplify a congenital defect, other than deficiencies of cyclooxygenase and thromboxane synthetase, by which thromboxane production may be impaired in platelets.     

Differentiation-linked changes in tyrosine phosphorylation, functional activity, and gene expression downstream from the granulocyte- macrophage colony-stimulating factor receptor

The HL-60 model of myeloid maturation was used to test whether changes in signaling from the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor accompany maturation-related changes in cellular responses to GM-CSF. Receptor expression, tyrosine phosphorylation, functional activity, and c-fos gene expression were measured. Functional GM-CSF receptors were present throughout differentiation as both uninduced and dimethyl sulfoxide (DMSO)-induced HL-60 cells responded to GM-CSF, albeit in different ways. Uninduced promyelocytes proliferated in response to GM-CSF, whereas DMSO-induced cells lost the capacity to proliferate but did respond with increased expression of beta 2-integrins, enhanced respiratory burst activity, and metabolism of arachidonic acid. GM-CSF-stimulated upregulation of c-fos mRNA expression was not detected in immature cells but developed after 2 to 4 days with DMSO in line with a marked increase in responsiveness to stimulation with phorbol ester, showing that increased expression of c- fos is predominantly a feature of mature phagocytes. GM-CSF stimulated the tyrosine phosphorylation of a broadly similar range of proteins in both uninduced and DMSO-treated HL-60 cells, but protein bands were more heavily phosphorylated in DMSO-induced cells. Phosphorylation was rapid in onset and very transient in immature cells. Phosphorylation of several proteins, in particular a 130-kD band, was more sustained in DMSO-induced cells. These differences in signaling were not because of numerical differences in receptors, because reduction of GM-CSF concentration to trigger equivalent numbers of high-affinity receptors delayed the onset of phosphorylation in DMSO-induced cells. We conclude that there are maturation-related changes in signaling downstream from the GM-CSF receptor.     

Two Examples of Anti-Leb Detectet in the Sera of Patients with the Lewis Phenotype Le(a+b-)

D'une manière générale, on décrit la présence d'anti-Le^b uniquement chez les personnes ayant le phénotype érythrocytaire Le(a-b-); mais, dans cet article, on décrit des exemples d'anti-Le^b se manifestant chez les personnes de phénotype Le(a + b-). Ces anticorps ont été trouvés chez des donneurs de groupe A₁ et avaient une spécificité Le^bH.

Zusammenfassung

Anti-Le^b kommt üblicherweise nur bei Individuen mit dem Phänotyp Le(a-b-) vor. In der vorliegenden Arbeit werden zwei Beispiele von Anti-Le^b-Antikörpern bei Personen mit dem Phänotyp Le(a+b-) beschrieben. Beide wurden bei Spendern mit der Grappe A₁ gefunden. Sie zeigten beide Le^bH-Spezifität.