Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection.

BACKGROUND: Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited. METHODS: We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)-based metabolites. RESULTS: Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = -0.35, P = .02; r = -0.40, P = .009, respectively), frontal white matter (r = -0.43, P = .003; r = -0.30, P = .048, respectively), and parietal gray matter (r = -0.43, P = .003; r = -0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups. CONCLUSIONS: Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation.

Risk Minimization in Scale-Up of Biomass and Waste Carbon Upgrading Processes.

Improving the odds and pace of successful biomass and waste carbon utilization technology scale-up is crucial to decarbonizing key industries such as aviation and materials within timelines required to meet global climate goals. In this perspective, we review deficiencies commonly encountered during scale-up to show that many nascent technology developers place too much focus on simply demonstrating that technologies work in progressively larger units ("profit") without expending enough up-front research effort to identify and derisk roadblocks to commercialization (collecting "information") to inform the design of these units. We combine this conclusion with economic and timeline data collected from technology scale-up and piloting operations at the National Renewable Energy Laboratory (NREL) to motivate a more scientific, risk-minimized approach to biomass and waste carbon upgrading scale-up. Our proposed approach emphasizes maximizing information collection in the smallest, most agile, and least expensive experimental setups possible, emulating the mentality embraced by R&D across the petrochemical industry. Key points are supported by examples of successful and unsuccessful scale-up efforts undertaken at NREL and elsewhere. We close by showing that the U.S. national laboratory system is uniquely well equipped to serve as a hub to facilitate effective scale-up of promising biomass and waste carbon upgrading technologies.

A Retrospective Analysis of Sacroiliac Joint Pain Interventions: Intraarticular Steroid Injection and Lateral Branch Radiofrequency Neurotomy.

BACKGROUND: Sacroiliac joint (SIJ) pain is a common etiology of chronic lower back pain. Treatment of persistent sacroiliac joint pain may entail intraarticular steroid injections and lateral branch radiofrequency neurotomy. OBJECTIVES: This study evaluates the efficacy of SIJ intervention treatments by comparing intraarticular steroid injections with lateral branch radiofrequency neurotomy. STUDY DESIGN: Retrospective cohort study. SETTING: We reviewed electronic medical records of patients with SIJ pain at Massachusetts General Hospital from 2006  through 2016 and identified 354 patients who received 930 SIJ intraarticular  injections and 19 patients who received 41 SIJ lateral branch radiofrequency neurotomies. METHODS: The Numeric Rating Scale (NRS) score for pain and the Eastern Cooperative Oncology Group (ECOG) Performance Status were measured prior to intervention and on follow-up. A mixed effects model was used to evaluate the duration of treatment effect. RESULTS: Patients who received an SIJ intraarticular steroid injection reported lower pain scores following treatment with a mean (standard deviation) NRS reduction from 6.77 (2.25) to 2.72 (2.81). SIJ lateral branch radiofrequency neurotomy resulted in NRS reduction from 5.96 (2.39) to 3.54 (3.14). A linear mixed model analysis suggests SIJ intraarticular steroid injections provided an estimated mean (CI 95%) of 38 (30-46.3) days of pain relief. Lateral branch radiofrequency neurotomy provided 82 (39.4-124.8) days of pain relief. The mean preprocedure ECOG score was 1.22 for both interventions and trended toward improvement with a post SIJ intraarticular injection score of 1.05 and SIJ lateral branch radiofrequency neurotomy score of 1.03. LIMITATIONS: There was variable follow-up reporting among patients. The small size of the lateral branch radiofrequency cohort limited intergroup comparisons. CONCLUSION: Both SIJ intraarticular steroid injections and SIJ lateral branch radiofrequency neurotomy demonstrated significant pain relief for patients with SIJ pain. SIJ lateral branch radiofrequency neurotomy provided a longer duration of pain relief (82 days) versus SIJ intraarticular steroid injection (38 days).

Clinical pathologic case report: A 70-year-old man with inflammatory cerebral amyloid angiopathy causing headache, cognitive impairment, and aphasia.

A 70-year-old man presented with two months of worsening cognitive impairment, hallucinations, and difficulty speaking, with superimposed headaches. Cerebrospinal fluid analysis was notable for lymphocytic pleocytosis and elevated protein. Imaging studies revealed multiple acute and subacute infarcts with cortical microhemorrhages. The patient underwent a stereotactic brain biopsy. In this article, we discuss the patient's differential diagnosis, pathologic findings, ultimate diagnosis, and clinical outcome.

Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death.

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection.

OBJECTIVE: We examined the longitudinal effects of primary HIV infection (PHI) and responses to early antiretroviral therapy (ART) on the brain using high-field magnetic resonance spectroscopy (MRS). METHODS: Cerebral metabolites were measured longitudinally with 4T proton MRS and assessed for ART effects in participants with PHI. Levels of glutamate (Glu), N-acetylaspartate (NAA), myo-inositol (MI), and choline-containing metabolites (Cho) were measured relative to creatine + phosphocreatine (Cr) in anterior cingulate, basal ganglia, frontal white matter, and parietal gray matter. RESULTS: Fifty-three participants recruited at median 3.7 months post HIV transmission were followed a median 6.0 months. A total of 23 participants initiated ART during follow-up. Prior to ART, increases per month were observed in Cho/Cr (slope = 0.0012, p = 0.005) and MI/Cr (slope = 0.0041, p = 0.005) in frontal white matter as well as increases in MI/Cr (slope = 0.0041, p < 0.001) and NAA/Cr (slope = 0.0024, p = 0.030) in parietal gray matter. After initiation of ART, prior positive slopes were no longer significantly different from zero, while Glu/Cr in basal ganglia decreased (slope = -0.0038, p = 0.031). CONCLUSIONS: Early in HIV infection, increases of Cho/Cr and MI/Cr in treatment-naive participants suggest progressive inflammation and gliosis in the frontal white matter and parietal gray matter, which is attenuated after initiation of ART. Elevated baseline Glu/Cr in basal ganglia may signal excitotoxicity; its subsequent stabilization and downward trajectory with ART may lend further support for early ART initiation.

Do increased summer precipitation and N deposition alter fine root dynamics in a Mojave Desert ecosystem?

Climate change is expected to impact the amount and distribution of precipitation in the arid southwestern United States. In addition, nitrogen (N) deposition is increasing in these regions due to increased urbanization. Responses of belowground plant activity to increases in soil water content and N have shown inconsistent patterns between biomes. In arid lands, plant productivity is limited by water and N availability so it is expected that changes in these factors will affect fine root dynamics. The objectives of this study were to quantify the effects of increased summer precipitation and N deposition on fine root dynamics in a Mojave Desert ecosystem during a 2-year field experiment using minirhizotron measurements. Root length density, production, and mortality were measured in field plots in the Mojave Desert receiving three 25 mm summer rain events and/or 40 kg N ha(-1)  yr(-1) . Increased summer precipitation and N additions did not have an overall significant effect on any of the measured root parameters. However, differences in winter precipitation resulting from interannual variability in rainfall appeared to affect root parameters with root production and turnover increasing following a wet winter most likely due to stimulation of annual grasses. In addition, roots were distributed more deeply in the soil following the wet winter. Root length density was initially higher under canopies compared to canopy interspaces, but converged toward the end of the study. In addition, roots tended to be distributed more deeply into the soil in canopy interspace areas. Results from this study indicated that increased summer precipitation and N deposition in response to climate change and urbanization are not likely to affect fine root dynamics in these Mojave Desert ecosystems, despite studies showing aboveground plant physiological responses to these environmental perturbations. However, changes in the amount and possibly distribution of winter precipitation may affect fine root dynamics.