BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p \u3c 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p \u3c 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored

Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis

Association between microvessel density (MVD) and tumor characteristics among breast cancer cases (n = 44). (DOC 54 kb

Relationship of Mammographic Density and Gene Expression: Analysis of Normal Breast Tissue Surrounding Breast Cancer

Previous studies of breast tissue gene expression have demonstrated that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density (MD) and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 breast cancer patients from the population-based Polish Women's Breast Cancer Study

Small RNAs with 5′-Polyphosphate Termini Associate with a Piwi-Related Protein and Regulate Gene Expression in the Single-Celled Eukaryote Entamoeba histolytica

Small interfering RNAs regulate gene expression in diverse biological processes, including heterochromatin formation and DNA elimination, developmental regulation, and cell differentiation. In the single-celled eukaryote Entamoeba histolytica, we have identified a population of small RNAs of 27 nt size that (i) have 5′-polyphosphate termini, (ii) map antisense to genes, and (iii) associate with an E. histolytica Piwi-related protein. Whole genome microarray expression analysis revealed that essentially all genes to which antisense small RNAs map were not expressed under trophozoite conditions, the parasite stage from which the small RNAs were cloned. However, a number of these genes were expressed in other E. histolytica strains with an inverse correlation between small RNA and gene expression level, suggesting that these small RNAs mediate silencing of the cognate gene. Overall, our results demonstrate that E. histolytica has an abundant 27 nt small RNA population, with features similar to secondary siRNAs from C. elegans, and which appear to regulate gene expression. These data indicate that a silencing pathway mediated by 5′-polyphosphate siRNAs extends to single-celled eukaryotic organisms

Surprises and Insights from Long-Term Aquatic Data Sets and Experiments

Long-term research on freshwater ecosystems provides insights that can be difficult to obtain from other approaches. Widespread monitoring of ecologically relevant water-quality parameters spanning decades can facilitate important tests of ecological principles. Unique long-term data sets and analytical tools are increasingly available, allowing for powerful and synthetic analyses across sites. Long-term measurements or experiments in aquatic systems can catch rare events, changes in highly variable systems, time-lagged responses, cumulative effects of stressors, and biotic responses that encompass multiple generations. Data are available from formal networks, local to international agencies, private organizations, various institutions, and paleontological and historic records; brief literature surveys suggest much existing data are not synthesized. Ecological sciences will benefit from careful maintenance and analyses of existing long-term programs, and subsequent insights can aid in the design of effective future long-term experimental and observational efforts. Long-term research on freshwaters is particularly important because of their value to humanity.Keywords: long term, lakes, data, freshwater, stream

Primary Human mDC1, mDC2, and pDC Dendritic Cells Are Differentially Infected and Activated by Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) causes recurrent infections throughout life. Vaccine development may depend upon understanding the molecular basis for induction of ineffective immunity. Because dendritic cells (DCs) are critically involved in early responses to infection, their interaction with RSV may determine the immunological outcome of RSV infection. Therefore, we investigated the ability of RSV to infect and activate primary mDCs and pDCs using recombinant RSV expressing green fluorescent protein (GFP). At a multiplicity of infection of 5, initial studies demonstrated ∼6.8% of mDC1 and ∼0.9% pDCs were infected. We extended these studies to include CD1c−CD141+ mDC2, finding mDC2 infected at similar frequencies as mDC1. Both infected and uninfected cells upregulated phenotypic markers of maturation. Divalent cations were required for infection and maturation, but maturation did not require viral replication. There is evidence that attachment and entry/replication processes exert distinct effects on DC activation. Cell-specific patterns of RSV-induced maturation and cytokine production were detected in mDC1, mDC2, and pDC. We also demonstrate for the first time that RSV induces significant TIMP-2 production in all DC subsets. Defining the influence of RSV on the function of selected DC subsets may improve the likelihood of achieving protective vaccine-induced immunity

Changes in timber haul emissions in the context of shifting forest management and infrastructure

<p>Abstract</p> <p>Background</p> <p>Although significant amounts of carbon may be stored in harvested wood products, the extraction of that carbon from the forest generally entails combustion of fossil fuels. The transport of timber from the forest to primary milling facilities may in particular create emissions that reduce the net sequestration value of product carbon storage. However, attempts to quantify the effects of transport on the net effects of forest management typically use relatively sparse survey data to determine transportation emission factors. We developed an approach for systematically determining transport emissions using: 1) -remotely sensed maps to estimate the spatial distribution of harvests, and 2) - industry data to determine landscape-level harvest volumes as well as the location and processing totals of individual mills. These data support spatial network analysis that can produce estimates of fossil carbon released in timber transport.</p> <p>Results</p> <p>Transport-related emissions, evaluated as a fraction of transported wood carbon at 4 points in time on a landscape in western Montana (USA), rose from 0.5% in 1988 to 1.7% in 2004 as local mills closed and spatial patterns of harvest shifted due to decreased logging on federal lands.</p> <p>Conclusion</p> <p>The apparent sensitivity of transport emissions to harvest and infrastructure patterns suggests that timber haul is a dynamic component of forest carbon management that bears further study both across regions and over time. The monitoring approach used here, which draws only from widely available monitoring data, could readily be adapted to provide current and historical estimates of transport emissions in a consistent way across large areas.</p