Vitamin D in SLE: a role in pathogenesis and fatigue? A review of the literature.

Fatigue is a common, disabling problem that is highly prevalent in patients with systemic lupus erythematous (SLE). More recently, vitamin D status has been established as a potential contributor to SLE pathogenesis and manifestations, in particular fatigue. This review summarizes the literature regarding the role of vitamin D in SLE, and provides an overview of the recent literature examining the association between vitamin D and fatigue in patients with SLE. Finally, the role of vitamin D supplementation in the treatment of SLE-related fatigue is considered.

Glutamine Imaging: A New Avenue for Glioma Management.

The glutamine pathway is emerging as an important marker of cancer prognosis and a target for new treatments. In gliomas, the most common type of brain tumors, metabolic reprogramming leads to abnormal consumption of glutamine as an energy source, and increased glutamine concentrations are associated with treatment resistance and proliferation. A key challenge in the development of glutamine-based biomarkers and therapies is the limited number of in vivo tools to noninvasively assess local glutamine metabolism and monitor its changes. In this review, we describe the importance of glutamine metabolism in gliomas and review the current landscape of translational and emerging imaging techniques to measure glutamine in the brain. These techniques include MRS, PET, SPECT, and preclinical methods such as fluorescence and mass spectrometry imaging. Finally, we discuss the roadblocks that must be overcome before incorporating glutamine into a personalized approach for glioma management.

Cardiac magnetic resonance imaging in patients with systemic lupus erythematosus.

OBJECTIVES: To delineate the cardiac magnetic resonance (MR) appearances of cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE), in comparison with transthoracic echocardiographs. METHODS: Cardiac MR was performed on 22 patients with SLE-11 with previous CVD and 11 matched controls-using late gadolinium contrast enhancement (LGE) to identify areas of myocardial scarring; Transthoracic echocardiography (TTE) was performed on the same day. RESULTS: Twenty female and two male patients participated. LGE was seen in 5/11 subjects in the CVD group (4/5 with previous myocardial infarction) and 1/11 in the control group. TTE detected myocardial abnormalities in 2/6 patients with LGE. CONCLUSION: The cardiac MR appearance of CVD in these patients with SLE was suggestive of coronary disease, rather than cumulative inflammatory muscle damage. Cardiac MR detected more abnormalities than TTE. Further studies of cardiac MR in patients with SLE are warranted to investigate these preliminary findings.

Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

Immunizing patients with systemic lupus erythematosus: a review of effectiveness and safety.

Concerns regarding the safety and efficacy of immunization in patients with SLE have persisted for over 60 years, despite the increased risk of infection in these patients. There are many anecdotal case reports of SLE induction or exacerbation following immunization, but overall, these events seem to be very rare. Evidence from prospective trials suggests that inactivated and component vaccines are probably safe in patients with SLE. Live vaccines are contraindicated in patients on immunosuppressive agents or high dose steroids (prednisone 20 mg/day or greater). There is limited evidence regarding efficacy of vaccination in patients with SLE. Studies assessing serological response to vaccination have generally shown that the majority of patients have an appropriate response, but a significant minority do not. Response to hepatitis B vaccination may be impaired and serological responses should be assessed post vaccination. It is not clear if disease activity or immunosuppressive medications are risk factors for a poor response, rather than intrinsic abnormalities of immune function in patients with SLE. The majority of patients appear to have a reasonable serological response to vaccination.

Indirect inputs to ventral temporal cortex of monkey: the influence of unit activity of alerting auditory input, interhemispheric subcortical visual input, reward, and the behavioral response.

1. This study examined nonvisual and indirect inputs to 1,021 single units recorded in inferotemporal and parahippocampal cortex of behaving macaques. 2. To better isolate these influences, a fully split-brain, split-chiasm preparation was used. Extracellular single-unit activity was recorded while the ipsilateral eye was covered. During the recordings the monkeys worked on a visual discrimination task that consisted of a series of presentations of single images. 3. When the interval between presentations was varied randomly (usually between 4 and 15 s) about one-quarter of these cells responded to an alerting tone sounded 500 ms before the onset of the visual image. That this response is due to the warning value of the tone was shown by finding that an identical tone sounded at the end of each trial produced no response from these cells. Use of an exchange between pairs of light-emitting diodes as a warning signal (one turned on as the other was turned off, also 500 ms before the visual stimulus onset) produced a similar response in many units. This indicates a subcortical route for the alerting signal. In most cases, warning responses were inhibitory, often delayed with respect to the warning signal occurrence to more nearly match the image arrival time. 4. Surprisingly, and despite the monkeys' confirmed split-brain status, occasional cells (approximately 2%) showed a response from a visual presentation limited to the other hemisphere. Although this subcortical visual input was far weaker than direct visual input, it was nonetheless statistically reliable. Importantly, the indirect input was stimulus specific and could form the neural basis for a limited interhemispheric visual transfer of the sort seen in human split-brain patients. 5. Also rarely, cells showed activity time locked to the animal's behavioral response.