Burkitt non-Hodgkin lymphoma presenting with mental neuropathy ('numb chin' syndrome) in an HIV-positive patient

Mental nerve neuropathy is usually due to local trauma or dental causes, but may be a manifestation of malignancy. A patient with virologically controlled human immunodeficiency virus (HIV) infection presented with a 'numb chin' on the background of long-standing night sweats, malaise and weight loss, worsening respiratory symptoms, and lymphadenopathy. Burkitt non-Hodgkin lymphoma was diagnosed from histology of a lymph node. Imaging (magnetic resonance imaging and18fluorodeoxyglucose [FDG]-positron emission tomography-computed tomography [PET-CT]) showed abnormal intracranial enhancement of the right mandibular nerve and extensive18FDG-avid lymphadenopathy above and below the diaphragm, focal lesions in the spleen and within the right mandible. The patient received chemotherapy and remains in clinical and radiological remission seven years later. This case highlights the need for clinicians to maintain a high index of suspicion for underlying malignancy when an HIV-infected patient presents with new onset of a 'numb chin'. Additionally, it demonstrates the importance of functional18FDG-PET-CT and neuroimaging in order to identify site(s) of pathology

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand

Cerebrospinal fluid biomarkers in cerebral amyloid angiopathy

BACKGROUND: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. METHODS: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. RESULTS: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ_{38}, Aβ_{40}, Aβ_{42}, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ_{38}, Aβ_{40}, Aβ_{42}, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ_{42}, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile. CONCLUSION: CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed

Occult hepatitis B virus infection: diagnosis, implications and management?

Occult hepatitis B virus (HBV) infection is generally defined as the detection of HBV-DNA in the serum or liver tissue of patients who test negative for hepatitis B surface antigen. In most cases, occult HBV infection is related to low level HBV infection with subdetectable levels of HBsAg and not infection with HBV variants that cannot express S proteins or produce S proteins with aberrant epitopes that are not detected by conventional serological assays. Prevalence of occult HBV infection is related to the overall prevalence of HBV infection in that country, being more common in persons with prior exposure to HBV. Occult HBV infection has been found in a substantial proportion of patients with cirrhosis and hepatocellular carcinoma but other causes of liver disease are frequently present. Future studies should focus on delineating the pathogenic role of occult HBV infection and the basis for failure to detect circulating hepatitis B surface antigen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75344/1/j.1440-1746.2004.03657.x.pd

Tonsillar ectopia in idiopathic scoliosis: does it play a role in the pathogenesis and prognosis or is it only an incidental finding?

ABSTRACT: BACKGROUND: There is an ongoing controversy about the significance of tonsillar ectopia among patients with idiopathic scoliosis (IS). AIM: To find out if tonsillar ectopia occurs more frequently among patients with IS and if it plays any etiological or prognostic role in IS. STUDY DESIGN: Retrospective study. METHODS: Retrospective analysis of 155 consecutive spine MRIs (79 patients with IS and 76 controls; aged 7-25 years; 55% were female) with regard to the position of the cerebellar tonsils in relation to foramen magnum and the sagittal diameter of foramen magnum. All images were evaluated independently by two neuroradiologists. Interobserver and intraobserver reliability analysis was performed by calculation of kappa-value, intraclass correlation coefficient, and systematic and random errors. The occurrence of tonsillar ectopia among patients with IS and controls was estimated and the association of tonsillar ectopia with different predictors has been tested. Statistical significance was set to P </= 0.05. RESULTS: The interobserver and intraobserver agreement with regard to the occurrence of tonsillar ectopia was almost perfect (kappa 0.84 and 0.89, respectively). Tonsillar ectopia was found in 37% of patients with IS compared with 13% among controls (p < 0.001 and odds ratio of 3.8, 95% CI 1.7-8.5). The occurrence of tonsillar ectopia was not associated with the severity of scoliotic deformity (p = 0.85), or rapid progression of scoliosis (p = 0.76). Neurological deficit occurs twice as frequently in patients with tonsillar ectopia as in those with no tonsillar ectopia. Two of five patients with tonsillar ectopia showed improvement of their neurological deficit after the surgical correction of scoliosis. CONCLUSION: As tonsillar ectopia is significantly more frequent among patients with IS and may exhibit some prognostic utility in patients with neurological deficit, we forward the hypothesis that tonsillar ectopia may play a role in the development of the deformity in some patients with IS. However, occurrence of tonsillar ectopia among 13% of controls precludes stating a definitive role of tonsillar ectopia in the pathogenesis of IS. Some patients with IS, tonsillar ectopia and neurological deficit showed neurological improvement following the surgical correction of scoliosis

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series

Background: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. Objectives: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. Method: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen’s kappa. Results: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0–0.25 for PCA to 0.29–0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. Conclusion: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practic

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Comparison of machine learning and semi-quantification algorithms for (I123)FP-CIT classification: the beginning of the end for semi-quantification?

Background Semi-quantification methods are well established in the clinic for assisted reporting of (I123) Ioflupane images. Arguably, these are limited diagnostic tools. Recent research has demonstrated the potential for improved classification performance offered by machine learning algorithms. A direct comparison between methods is required to establish whether a move towards widespread clinical adoption of machine learning algorithms is justified. This study compared three machine learning algorithms with that of a range of semi-quantification methods, using the Parkinson’s Progression Markers Initiative (PPMI) research database and a locally derived clinical database for validation. Machine learning algorithms were based on support vector machine classifiers with three different sets of features: Voxel intensities Principal components of image voxel intensities Striatal binding radios from the putamen and caudate. Semi-quantification methods were based on striatal binding ratios (SBRs) from both putamina, with and without consideration of the caudates. Normal limits for the SBRs were defined through four different methods: Minimum of age-matched controls Mean minus 1/1.5/2 standard deviations from age-matched controls Linear regression of normal patient data against age (minus 1/1.5/2 standard errors) Selection of the optimum operating point on the receiver operator characteristic curve from normal and abnormal training data Each machine learning and semi-quantification technique was evaluated with stratified, nested 10-fold cross-validation, repeated 10 times. Results The mean accuracy of the semi-quantitative methods for classification of local data into Parkinsonian and non-Parkinsonian groups varied from 0.78 to 0.87, contrasting with 0.89 to 0.95 for classifying PPMI data into healthy controls and Parkinson’s disease groups. The machine learning algorithms gave mean accuracies between 0.88 to 0.92 and 0.95 to 0.97 for local and PPMI data respectively. Conclusions Classification performance was lower for the local database than the research database for both semi-quantitative and machine learning algorithms. However, for both databases, the machine learning methods generated equal or higher mean accuracies (with lower variance) than any of the semi-quantification approaches. The gain in performance from using machine learning algorithms as compared to semi-quantification was relatively small and may be insufficient, when considered in isolation, to offer significant advantages in the clinical context

The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought

Associations between Body Mass and the Outcome of Surgery for Scoliosis in Chinese Adults

BACKGROUND: In this study we intended to prove that being overweight has an unfavorable impact on the surgical treatment outcome of adult idiopathic scoliosis (AdIS). METHODS: This is a retrospective study on the surgical treatment of seventy-one more than 30 years old (58 females and 13 males; mean age 42.9±12.2) idiopathic scoliotic patients with a minimum follow up of at least 2 years. The patients were divided into an overweight group (BMI≥23) and a non-overweight group (BMI<23). Preoperative, postoperative first erect and final follow-up radiographic measures, perioperative data, the Oswestry disability index (ODI), and the visual analog scale (VAS) were reviewed and compared. FINDINGS: In the overweight group, no significant differences in radiographic measures, perioperative data, preoperative comorbidities, or postoperative complications, except for the more frequent concomitance of preoperative thoracic kyphosis 37.9±7.7 vs. 26.5±11.8 (P = 0.000) and thoracolumbar kyphosis 14.9±10.1 overweighted group vs. 6.5±9.9 non-overweighted group respectively (P = 0.002) were found. A higher morbidity of hypertension 36.8% vs. 9.6% (P = 0.004) was also observed in the overweight group. Postoperative ODI and VAS improved significantly in both groups compared to pre-operative values. The postoperative ODI of the overweight group (19.6±12.4) was significantly higher than that of the non-overweight group (12.4±7.9) (P = 0.022). CONCLUSIONS: Overweight adult idiopathic scoliotic patients had more frequent concomitance of preoperative thoracic kyphosis and thoracolumbar kyphosis and more serious postoperative pain. However, BMI did not affect the outcomes of surgical correction for coronal and sagittal scoliotic deformity and their postoperative complication rates were not significantly affected