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25 result(s) for "Bouffard, Marc A"
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FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch
Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7, a brain-FABP, maintains metabolic function in astrocytes and neural stem cells, but the effect of FABP7 on monocytes is unknown. Here we find elevated levels of FABP7 in the serum and cerebrospinal fluid of patients with secondary progressive MS. Elevated serum FABP7 levels positively correlate with higher disability scores, brain lesion volumes, and lower brain volumes. FABP7 levels are increased in astrocytes from MS postmortem brain lesion. Mechanistically, in vitro treatment of FABP7 induces CD16, CD80 and IL-1β expression in monocytes via increased glycolysis. FABP7-induced gene expression reflects enhanced inflammation, chemotaxis and glucose metabolism in monocytes. In conclusion, we find that FABP7 induces pro-inflammatory profiles in monocytes, correlates with disability and represents a potential biomarker and therapeutic target for progressive MS. While immune dysregulation is acknowledged as causal for multiple sclerosis (MS), how monocytes contribute to MS etiology is still unclear. Here the authors analyze peripheral blood and cerebrospinal fluid samples as well as brain MRI image data from MS patients to implicate FABP7 in alteration of monocyte glycolysis, and as a potential marker for MS progression.
Fulminant Idiopathic Intracranial Hypertension
Purpose of ReviewThe goal of this review is to describe the presenting features of fulminant idiopathic intracranial hypertension (IIH) and outline the multimodal approach to its treatment.Recent FindingsVenous sinus stenting may be an appropriate alternative to optic nerve sheath fenestration or cerebrospinal fluid shunting in select patients with fulminant IIH. Prompt surgical intervention maximizes the chance of visual recovery in patients with fulminant IIH.Summary“Fulminant IIH” is defined as intracranial hypertension with no secondary cause, severe vision loss within 4 weeks of symptom onset, and progressive vision loss over days. Rapid recognition of the fulminant phenotype of IIH by emergency department physicians, neurologists, and ophthalmologists is critical. Without appropriate triage and rapid medical and surgical intervention, patients with fulminant IIH are at high risk for profound, permanent vision loss. Prompt surgical intervention with optic nerve sheath fenestration, cerebrospinal fluid shunting, or venous sinus stenting minimizes the chance of poor visual outcome. If a delay is anticipated, serial lumbar punctures or temporary cerebrospinal fluid drainage and medical therapy may forestall irreversible vision loss.
Case 6-2021: A 65-Year-Old Man with Eye Pain and Decreased Vision
A 65-year-old man with Waldenström’s macroglobulinemia was evaluated because of an 8-day history of bilateral eye pain and decreased vision. He had decreased visual acuity, dyschromatopsia, visual field loss, a relative afferent pupillary defect, and an abnormal appearance of the optic disk. A diagnosis was made.
Mercury transport and human exposure from global marine fisheries
Human activities have increased the global circulation of mercury, a potent neurotoxin. Mercury can be converted into methylmercury, which biomagnifies along aquatic food chains and leads to high exposure in fish-eating populations. Here we quantify temporal trends in the ocean-to-land transport of total mercury and methylmercury from fisheries and we estimate potential human mercury intake through fish consumption in 175 countries. Mercury export from the ocean increased over time as a function of fishing pressure, especially on upper-trophic-level organisms. In 2014, over 13 metric tonnes of mercury were exported from the ocean. Asian countries were important contributors of mercury export in the last decades and the western Pacific Ocean was identified as the main source. Estimates of per capita mercury exposure through fish consumption showed that populations in 38% of the 175 countries assessed, mainly insular and developing nations, were exposed to doses of methylmercury above governmental thresholds. Our study shows temporal trends and spatial patterns of Hg transport by fisheries. Given the high mercury intake through seafood consumption observed in several understudied yet vulnerable coastal communities, we recommend a comprehensive assessment of the health exposure risk of those populations.
Infarction with associated pseudosarcomatous changes mimics anaplasia in otherwise grade I meningiomas
We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas. The described cases ( n  = 9) all demonstrated a discrete spindle-cell (pseudosarcomatous) component with brisk mitotic activity (12–14 mitoses/10 HPF), elevated Ki-67 (mean 75.5 ± 25.0%, quantified), absence of PR, SSTR2A, or EMA expression, and potential SMA expression (50%). Despite these high-grade features, all nine patients remained free of progression or recurrence post resection (follow-up mean: 49.8 months). In contrast, among a comparison (control) cohort of consecutive WHO grade II and III meningiomas ( n  = 16), as expected, progression rate was high (68.8%, P  = 0.002, Fisher’s exact, average time to progression = 25 months, follow-up mean: 39.8 months). While necrosis was a frequent feature among atypical/anaplastic meningiomas (12/16, 75%), and elevated mitoses and proliferative index were present consistent with histologic grade, a well-defined zonal pattern with pseudosarcomatous component was not present among these tumors. DNA methylation-based analysis readily distinguished meningiomas by copy number profiles and DNA-based methylation meningioma random forest classification analysis (meningioma v2.4 classifier developed at University of Heidelberg); all pseudosarcomatous cases analyzed (4/9) matched with high level calibrated classifier score to “MC benign-1”, with isolated loss of chromosome 22q identified as the sole copy number alteration. In contrast, multiple chromosomal losses were detected among the comparison cohort and classifier results demonstrated good concordance with histologic grade. Our findings suggest that pseudosarcomatous alterations represent reactive changes to central meningioma infarction, rather than focal anaplasia, and further support the use of DNA methylation-based analysis as a useful adjunct for predicting meningioma behavior. These indolent tumors should be distinguished from their atypical and anaplastic counterparts.
A Prospective Randomized Trial of Prognostic Genicular Nerve Blocks to Determine the Predictive Value for the Outcome of Cooled Radiofrequency Ablation for Chronic Knee Pain Due to Osteoarthritis
Abstract Background and Objectives Genicular nerve radiofrequency ablation is an effective treatment for patients with chronic pain due to knee osteoarthritis; however, little is known about factors that predict procedure success. The current study evaluated the utility of genicular nerve blocks to predict the outcome of genicular nerve cooled radiofrequency ablation (cRFA) in patients with osteoarthritis. Methods This randomized comparative trial included patients with chronic knee pain due to osteoarthritis. Participants were randomized to receive a genicular nerve block or no block prior to cRFA. Patients receiving a prognostic block that demonstrated ≥50% pain relief for six hours received cRFA. The primary outcome was the proportion of participants with ≥50% reduction in knee pain at six months. Results Twenty-nine participants (36 knees) had cRFA following a prognostic block, and 25 patients (35 knees) had cRFA without a block. Seventeen participants (58.6%) in the prognostic block group and 16 (64.0%) in the no block group had ≥50% pain relief at six months (P = 0.34). A 15-point decrease in the Western Ontario and McMaster Universities Osteoarthritis Index at six months was present in 17 of 29 (55.2%) in the prognostic block group and 15 of 25 (60%) in the no block group (P = 0.36). Conclusions This study demonstrated clinically meaningful improvements in pain and physical function up to six months following cRFA. A prognostic genicular nerve block using a local anesthetic volume of 1 mL at each injection site and a threshold of ≥ 50% pain relief for subsequent cRFA eligibility did not improve the rate of treatment success.
Requirements for a Coastal Hazards Observing System
Coastal zones are highly dynamical systems triggered by a variety natural and anthropogenic forcing factors, that include sea level rise, extreme events, local oceanic and atmospheric processes, ground subsidence, etc. However so far, they remain poorly monitored on a global scale. To better understand changes affecting world coastal zones and to provide crucial information to decision-makers involved in adaptation to and mitigation of environmental risks, coastal observations of various types need to be collected and analyzed. In this white paper, we first discuss the main forcing agents acting on coastal regions (e.g., sea level, winds, waves and currents, river runoff, sediment supply and transport, vertical land motions, land use) and the induced coastal response (e.g., shoreline position, estuaries morphology, land topography at the land-sea interface and coastal bathymetry). We identify a number of space-based observational needs that have to be addressed in the near future to understand coastal zone evolution. Among these, improved monitoring of coastal sea level by satellite altimetry techniques is recognized as high priority. Classical altimeter data in the coastal zone are adversely affected by land contamination with degraded range and geophysical corrections. However, recent progress in coastal altimetry data processing and multi-sensor data synergy, offers new perspective to measure sea level change very close to the coast. This issue is discussed in much detail in this paper, including the development of a global coastal sea-level and sea state climate record with mission consistent coastal processing and products dedicated to coastal regimes. Finally, we present a new promising technology based on the use of Signals of Opportunity (SoOps), i.e., communication satellite transmissions that are reutilized as illumination sources in a bistatic radar configuration, for measuring coastal sea level. Since SoOp technology requires only receiver technology to be placed in orbit, small satellite platforms could be used, enabling a constellation to achieve high spatio-temporal resolutions of sea level in coastal zones.
Where is 'where' in the human auditory cortex?
We examine the functional characteristics of auditory cortical areas that are sensitive to spatial cues in the human brain, and determine whether they can be dissociated from parietal lobe mechanisms. Three positron emission tomography (PET) experiments were conducted using a speaker array permitting quasi free-field sound presentation within the scanner. Posterior auditory cortex responded to sounds that varied in their spatial distribution, but only when multiple complex stimuli were presented simultaneously, implicating this cortical system in disambiguation of overlapping auditory sources. We also found that the right inferior parietal cortex is specifically recruited in localization tasks, and that its activity predicts behavioral performance, consistent with its involvement in sensorimotor integration and spatial transformation. These findings clarify the functional roles of posterior auditory and parietal cortices, and help to reconcile competing models of auditory cortical organization.
Does musculoskeletal pain interfere with motor learning in a gait adaptation task? A proof-of-concept study
Background Experimental pain during gait has been shown to interfere with learning a new locomotor task. However, very few studies have investigated the impact of clinical pain on motor learning due to the challenges associated with clinical populations. Objective The first objective of this proof-of-concept study was to determine the feasibility to obtain two groups of participants with chronic ankle pathology with or without residual pain while walking. The second objective was to evaluate the impact of clinical musculoskeletal pain on motor learning during gait. Methods Participants with chronic isolated ankle pathology were recruited and their personal and clinical characteristics were collected (functional performance, dorsiflexion maximal strength, range of motion). To assess motor acquisition (Day 1) and retention (Day 2), participants performed an adaptation task on two consecutive days that consisted of walking while experiencing a perturbing force applied to the ankle. The level of pain during the task was measured, and participants who reported pain were attributed to the Pain group and participants without pain to the No Pain group. Learning performance was assessed by measuring ankle kinematics (Mean plantarflexion absolute error) and learning strategy was assessed by measuring the Relative timing of error and the tibialis anterior (TA) electromyographic activity. Results Twenty-five participants took part in the experiment. Eight (32%) were excluded because they could not be included in either the Pain or No Pain group due to the intermittent pain, leaving eight participants in the Pain group and nine in the No Pain group. Both groups were similar in terms of baseline characteristics. Musculoskeletal pain had no influence on learning performance, but the learning strategy were different between the two groups. The No Pain group showed a TA activity reduction before perturbation between the days, while the Pain group did not. Conclusion Some barriers were identified in studying musculoskeletal pain including the high rates of participants’ exclusion, leading to a small sample size. However, we showed that it is feasible to investigate clinical pain and motor learning. From the results of this study, musculoskeletal pain has no influence on motor learning performance but influences the learning strategy.