Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density ...index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer's disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer's dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R
of free water and neurite density = 8.3%) and MMSE performance (8.2%) which was comparable to amyloid PET (7.4% for global cognition and 6.6% for memory). In the AD dementia cohort, tau deposition was the greatest contributor to cognitive performance (9.6%), but there was also a non-trivial contribution of the temporal white matter component (8.5%) to cognitive performance. The differences observed between the two cohorts were reflective of their distinct clinical composition. White matter microstructural damage assessed using advanced diffusion models may add significant value for distinguishing the underlying substrate (whether cerebrovascular disease versus neurodegenerative disease caused by tau deposition or TDP-43 pathology) for cognitive impairment in older adults.
Resistance in Vancomycin-Resistant Enterococci Miller, William R; Murray, Barbara E; Rice, Louis B ...
Infectious disease clinics of North America,
12/2020, Letnik:
34, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Serious infections owing to vancomycin-resistant enterococci have historically proven to be difficult clinical cases, requiring combination therapy and management of treatment-related toxicity. ...Despite the introduction of new antibiotics with activity against vancomycin-resistant enterococci to the therapeutic armamentarium, significant challenges remain. An understanding of the factors driving the emergence of resistance in vancomycin-resistant enterococci, the dynamics of gastrointestinal colonization and microbiota-mediated colonization resistance, and the mechanisms of resistance to the currently available therapeutics will permit clinicians to be better prepared to tackle these challenging hospital-associated pathogens.
Vancomycin-resistant enterococci Murray, Barbara E.
The American journal of medicine,
03/1997, Letnik:
102, Številka:
3
Journal Article
Recenzirano
Enterococci have been recognized as an important cause of nosocomial infections for almost 20 years and as a cause of endocarditis for almost a century. While long known for their capacity of ...displaying multiple antibiotic resistant traits, the extent to which this could occur was not fully appreciated until the emergence of enterococci with acquired resistance to vancomycin; this resistance has been particularly problematic because it often occurs in the uncommon subset of enterococci that are also highly resistant to ampicillin—a combination with devastating therapeutic consequences. The observation that vancomycin resistance can be transferred to and expressed in other gram-positive organisms, for which vancomycin is often considered the primary therapeutic alternative, is a chilling reminder of just how close we may be to a wide array of potentially untreatable “killer” microbes.
Lake Vida, located in Victoria Valley, is one of the largest lakes in the McMurdo dry valleys and is known to contain hypersaline liquid brine sealed below 16 m of freshwater ice. For the first time, ...Lake Vida was drilled to a depth of 27 m. Below 21 m the ice is marked by well-sorted sand layers up to 20 cm thick within a matrix of salty ice. From ice chemistry, isotopic composition of δ18O and δ2H, and ground penetrating radar profiles, we conclude that the entire 27 m of ice formed from surface runoff and the sediment layers represent the accumulation of surface deposits. Radiocarbon and optically stimulated luminescence dating limit the maximum age of the lower ice to 6300 14C yr BP. As the ice cover ablated downwards during periods of low surface inflow, progressive accumulation of sediment layers insulated and preserved the ice and brine beneath, analogous to the processes that preserve shallow ground ice. The repetition of these sediment layers reveals hydrologic variability in Victoria Valley during the mid- to late Holocene. Lake Vida is an exemplar site for understanding the preservation of subsurface brine, ice, and sediment in a cold desert environment.
Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ...ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.
Iron deficiency anemia (IDA) affects 2%-5% of reproductive-age women. Screening is based on risk factors, such as a low-iron diet and menstruation. However, published IDA risk factors fail to ...consider age-related risks specific to adolescent women, potentially limiting identification of high-risk adolescents for objective testing. The goal of the study was to examine IDA risk factors in a nationally representative sample of younger (12-21 years) and older (22-49 years) reproductive-age women.
Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. IDA was defined using hemoglobin, ferritin, soluble transferrin receptor, standard NHANES laboratory measures. Sex-, age-, and race-specific hemoglobin values defined anemia. Iron deficiency was calculated using ferritin and soluble transferrin receptor in the body iron formula. Logistic regression assessed the association of potential risk factors (race, body mass index, poverty, iron intake, tobacco/nicotine exposure, physical activity, menses, and contraceptive use) with IDA in younger and older women.
The prevalence of IDA was 2.4% and 5.5% among younger and older women, respectively. Among younger women, contraceptive use was marginally protective from IDA (risk ratio 0.50, 95% confidence interval CI 0.25-1.00). Among older women, significant variables included Black race (risk ratio 2.31, 95% CI 1.33-4.02) and increased years menstruating (≥25 years vs. <25 years; risk ratio 1.93, 95% CI 0.99-3.76).
Risk factors for IDA among older reproductive-age women do not apply to adolescent women. To better inform the timing and frequency of screening recommendations, further research must identify adolescent-specific IDA risk factors.
Abstract Background Extra-appendiceal colonic carcinoids are uncommon neuroendocrine tumors with a poor prognosis compared with carcinoids of other gastrointestinal origins. Few studies have examined ...the clinicopathologic profile and behavior of this rare tumor. Materials and methods A retrospective analysis was performed on patients with colonic carcinoid tumors evaluated at a single tertiary care center between 1996 and 2012. Collected data included patient and tumor characteristics, presentation, treatment, recurrence, and survival. Results were integrated into a comprehensive review of the colonic carcinoid literature. Results In total, 114 patients with colorectal carcinoid tumors were identified, and 15 patients with extra-appendiceal tumors were analyzed. The mean age was 58.6 ± 3.0 y, and subjects were predominantly male (73.3%). The most common presenting problem was abdominal pain (33.3%), although 26.7% of patients were asymptomatic. Cecal tumors were the most prevalent (73.3%), and most patients underwent right hemicolectomy. Three patients with lesions < 1 cm were treated endoscopically. The mean tumor diameter was 2.9 ± 0.5 cm, with lymph node or distant metastasis present in 53.3% and 26.7%, respectively. All but two patients underwent a presumed curative resection. During a mean follow-up of 4.2 ± 1.0 y, there was only one death (non–carcinoid specific). Eleven patients were alive without evidence of disease at last follow-up and three patients were alive with disease, one of whom initially had a presumed curative resection that recurred. Conclusions This case series further elucidates the clinicopathologic characteristics of colonic carcinoid tumors, which aids physicians in guiding the diagnosis and management of these rare tumors.
Previously, in our laboratory, we established a two-chamber system to study translocation of Enterococcus faecalis across monolayers of polarized human colon carcinoma-derived T84 cells. By using the ...same system in the present study, we now show that disruption of gelE of strain OG1RF, which also has a polar effect on the cotranscribed sprE, as well as disruption of its regulatory system (fsrA, fsrB, and fsrC) resulted in a loss of detectable translocation by E. faecalis OG1RF; these mutants lost gelatinase (GelE) and serine protease (SprE) production by standard assay. A gelE deletion mutant of OG1RF (GelE⁻ SprE⁺) also showed that significantly reduced translocation and complementation with the gelE gene (pTEX5438) in trans restored gelatinase and translocation, demonstrating that gelatinase is important for E. faecalis translocation. Complementation of fsrA, fsrB, and fsrC mutants with all three fsr genes also resulted in production of gelatinase and translocation. Furthermore, introduction of fsr genes into two non-gelatinase-producing E. faecalis isolates, the well-characterized laboratory strain JH2-2 and a human-derived fecal isolate, TX1322 (both of which have gelE but not fsrA or fsrB, are gelatinase negative, and do not translocate), resulted in gelatinase production by these strains and restored translocation across T84 monolayers, while transformation with pTEX5438 (gelE) showed little or no translocation and no detectable gelatinase, confirming the importance of both fsr and gelatinase for E. faecalis translocation. The importance of gelatinase production was also corroborated among 20 E. faecalis human isolates (7 fecal, 7 endocarditis, and 6 urine isolates), which showed translocation by all gelatinase-positive isolates but little to no translocation for gelatinase nonproducers. These results indicate that gelatinase is important for the successful in vitro translocation of E. faecalis across human enterocyte-like T84 cells.
The Antarctic marine ecosystem harbors a wealth of biological and chemical innovation that has risen in concert over millennia since the isolation of the continent and formation of the Antarctic ...circumpolar current. Scientific inquiry into the novelty of marine natural products produced by Antarctic benthic invertebrates led to the discovery of a bioactive macrolide, palmerolide A, that has specific activity against melanoma and holds considerable promise as an anticancer therapeutic. While this compound was isolated from the Antarctic ascidian Synoicum adareanum, its biosynthesis has since been hypothesized to be microbially mediated, given structural similarities to microbially produced hybrid nonribosomal peptide-polyketide macrolides. Here, we describe a metagenome-enabled investigation aimed at identifying the biosynthetic gene cluster (BGC) and palmerolide A-producing organism. A 74-kbp candidate BGC encoding the multimodular enzymatic machinery (hybrid type I-
-AT polyketide synthase-nonribosomal peptide synthetase and tailoring functional domains) was identified and found to harbor key features predicted as necessary for palmerolide A biosynthesis. Surveys of ascidian microbiome samples targeting the candidate BGC revealed a high correlation between palmerolide gene targets and a single 16S rRNA gene variant (
= 0.83 to 0.99). Through repeated rounds of metagenome sequencing followed by binning contigs into metagenome-assembled genomes, we were able to retrieve a nearly complete genome (10 contigs) of the BGC-producing organism, a novel verrucomicrobium within the
family that we propose here as "
Synoicihabitans palmerolidicus." The refined genome assembly harbors five highly similar BGC copies, along with structural and functional features that shed light on the host-associated nature of this unique bacterium.
Palmerolide A has potential as a chemotherapeutic agent to target melanoma. We interrogated the microbiome of the Antarctic ascidian, Synoicum adareanum, using a cultivation-independent high-throughput sequencing and bioinformatic strategy. The metagenome-encoded biosynthetic machinery predicted to produce palmerolide A was found to be associated with the genome of a member of the S. adareanum core microbiome. Phylogenomic analysis suggests the organism represents a new deeply branching genus, "
Synoicihabitans palmerolidicus," in the
family of the
phylum. The
. Synoicihabitans palmerolidicus 4.29-Mb genome encodes a repertoire of carbohydrate-utilizing and transport pathways, a chemotaxis system, flagellar biosynthetic capacity, and other regulatory elements enabling its ascidian-associated lifestyle. The palmerolide producer's genome also contains five distinct copies of the large palmerolide biosynthetic gene cluster that may provide structural complexity of palmerolide variants.
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