Occlusion of the AOP results in a characteristic pattern of ischemia: bilateral paramedian thalamus with or without midbrain involvement. Although the classic imaging findings are often recognized, ...only a few small case series and isolated cases of AOP infarction have been reported. The purpose of this study was to characterize the complete imaging spectrum of AOP infarction on the basis of a large series of cases obtained from multiple institutions.
Imaging and clinical data of 37 patients with AOP infarction from 2000 to 2009 were reviewed retrospectively. The primary imaging criterion for inclusion was an abnormal signal intensity on MR imaging and/or hypoattenuation on CT involving distinct arterial zones of the bilateral paramedian thalami with or without rostral midbrain involvement. Patients were excluded if there was a neoplastic, infectious, or inflammatory etiology.
We identified 4 ischemic patterns of AOP infarction: 1) bilateral paramedian thalamic with midbrain (43%), 2) bilateral paramedian thalamic without midbrain (38%), 3) bilateral paramedian thalamic with anterior thalamus and midbrain (14%), and 4) bilateral paramedian thalamic with anterior thalamus without midbrain (5%). A previously unreported finding (the "V" sign) on FLAIR and DWI sequences was identified in 67% of cases of AOP infarction with midbrain involvement and supports the diagnosis when present.
The 4 distinct patterns of ischemia identified in our large case series, along with the midbrain V sign, should improve recognition of AOP infarction and assist with the neurologic evaluation and management of patients with thalamic strokes.
This paper focused on the biodistribution of the cross-linked hyaluronic acid (HA-NPs) sub-micron particles in tumor-bearing mice. Solvent-non solvent method followed glutaraldehyde cross-linking ...utilized for the fabrication of HA-NPs. Size measurement and morphological analysis were performed by dynamic light scattering and electron microscopy, respectively and the size found to be in the range of 200–400 nm. In vitro viability in LNCaP cell line was assessed by water soluble tetrazolium assay after 24 h of exposure to sub-micron particles and no toxicity was found to higher concentration of 3 mg/mL. Internalization of particles in prostate cancer cell LNCaP were studied by confocal microscopy with FITC labeled submicron particles and involvement of hyaluronan receptor mediated uptake/endocytosis was confirmed by competitive assay. Biodistribution studies were performed in xenograft prostate cancer mice model with fluorophore labeled particles and monitored in tumoral parenchyma with strong fluorescence, meanwhile very less signal in liver, kidney and spleen while no fluorescence found in lung after 24 h of systemic administration; that shown ability of this HA based system to recognize cancer tissue. These result fetched that hyaluronic acid based system is selective for tumoral site and can be utilized to deliver bioactives in specific (targeting) and controlled (temporal) manner to cancerous tissue.
Summary
Forefields of retreating glaciers represent unique opportunities to investigate the initial phases of soil formation and microbial interactions with mineral surfaces. An open question ...concerns the physical and chemical driving‐factors affecting the establishment of microbial communities in these young ecosystems. In this study we compared the bacterial community structure of six glacier forefield soils belonging to two contrasting bedrock categories (calcareous and siliceous) through T‐RFLP profiling of the 16S rRNA gene. The community profiles were correlated with an array of physical (soil texture, water holding capacity, hours of sunshine, temperature, rainfall and exposure) and chemical (TC, TN, DOC, extractable nutrients and pH) factors using canonical correspondence analysis (CCA). A first comparison of the T‐RFLP profiles suggested that the degree of operational taxonomic unit (OTU) diversity of these soils was similar, and that community structure was dominated by ubiquitous taxa. CCA showed that both physical (e.g. hours of sunshine or rainfall) and chemical factors (e.g. SO2−4 or PO3−4) played an equal role in shaping the soil bacterial communities. OTUs unique to specific sites appeared to be strongly influenced by the climatic regime and by texture. Overall, the community structure of the six glacial forefields showed no clear dependence on the bedrock categories.
HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is ...complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, β-amiloid
42
, neopterin, S100β), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman’s rho and Mann–Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4
+
T-lymphocyte were 10 years (5.5–15) and 691/uL (477–929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity parietal (rho 0.579;
p
< 0.001), occipital (rho 0.493;
p
= 0.007), and global sources (rho 0.464
p
= 0.011). Seven patients (12.9%) showed an abnormal neopterin level (> 1.5 ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (
p
values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.
The incidence of cardiovascular disorders in people living with HIV (PLWH) is higher than that in non-infected individuals. Traditional and specific risk factors have been described but the role of ...the gut microbiota-dependent choline metabolite, trimethylamine-N-oxide (TMAO) is still unclear.
A cross-sectional analysis and a longitudinal analysis (with high-dose probiotic supplementation) were performed to measure serum TMAO concentrations through UHPLC-MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non-parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used.
A total of 175 participants were enrolled in the study. Median serum TMAO concentrations were 165 (103-273) ng/mL. An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed; at linear logistic regression analysis, multimorbidity was the only independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 (0.71-1.21) mm, with a trend towards higher TMAO concentrations observed in patients with IMT >0.9 mm (P=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significantly change after 24 weeks (Wilcoxon paired P=0.220).
Serum TMAO levels in PLWH were associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis and were not affected by 6 months of high-dose probiotic supplementation.
Abstract
Objectives
An unexpected drug–drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential ...underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid.
Methods
We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs.
Results
One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45–56) and 23.4 kg/m2 (20.8–26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations median (IQR) = 132 ng/mL (62–227) in individuals on valproic acid versus 760 ng/mL (333–1407) in those not receiving valproic acid.
Conclusions
Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug–drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction.
Over the past decade, endovascular therapy has emerged as a promising therapeutic approach for select patients with acute ischemic stroke. However, the morbidity, mortality, and complication rates in ...intra-arterial recanalization trials are higher than in the National Institute of Neurological Disorders and Stroke trial of IV tissue plasminogen activator. This review discusses common complications associated with endovascular therapy for acute ischemic stroke, avoidance of complications, and management of some of the common complications.
► We analyzed the structure and activities of microbial communities in two different unvegetated glacier forefields throughout three seasons. ► Nutrient status at both sites changed during the three ...sampling seasons. ► Microbial community structures appeared affected by change in climate. ► Viable microbial communities did not change significantly.
This study addresses the relationship between the dynamical changes of soil properties and of the viable bacterial communities in the unvegetated forefields of two receding glaciers, Damma and Tsanfleuron (Switzerland).
In spring, summer and autumn, the soils were characterized in terms of their pH, TC, TN and soluble nutrients. Bacterial community structures were assessed through terminal restriction fragment length polymorphism (T-RFLP) profiling of the bacterial 16S rRNA at both the DNA and RNA level (RT-T-RFLP), and through the creation of cDNA-based clone libraries. In addition, the general activities of the communities were analyzed through enzymatic assays.
In general, while TC and TN varied only slightly between the seasons, the extractable nutrients had significantly lower concentrations in summer. Canonical correspondence analysis (CCA) showed clear correlations between bacterial community structures at each sampling season and environmental parameters. Climatic factors such as temperature, precipitation and sun hours appeared to be the most strongly correlated with the T-RFLP profiles. Investigation of RT-T-RFLP and cDNA-based clone libraries did not show marked changes of the viable members of the bacterial community. The class of α-Proteobacteria was the dominant bacterial component throughout the year in the profiles, suggesting that they are not strongly affected by seasonal change. However, other important groups such as Actinobacteria and Firmicutes showed changes in relative abundance and composition. Our results suggest that unvegetated glacier forefields experience temporal physico-chemical variations which may not affect the dominant viable components of the bacterial communities.
Limited data exist to guide patient selection for preventive treatment of unruptured cerebral aneurysms. Cerebral aneurysms have been associated with circle of Willis anomalies but whether this ...association is also related to aneurysm rupture is not known. The occurrence of cerebral aneurysm rupture when a circle of Willis anomaly was present or absent was compared.
Patients admitted over a 2 year period with a diagnosis of a cerebral aneurysm and an anterior communicating artery (ACoA) or posterior communicating artery (PCoA) aneurysm were included in the analysis. Brain vascular imaging was reviewed for aneurysm size, morphology and presence of circle of Willis anomaly. Relevant medical history and demographics were obtained from the medical records.
Of the 113 patients with ACoA or PCoA aneurysms, 85 (75.2%) cases were ruptured. There were 49 (43.4%) PCoA aneurysms and 64 (56.6%) ACoA aneurysms. Mean aneurysm size was 5.65 mm (SD 3.31). A circle of Willis anomaly was identified in 46 (40.7%) of all patients. Circle of Willis anomalies were present in 38 (46.9%) ruptured aneurysm cases and eight (29.6%) unruptured aneurysm cases. Multivariate analysis revealed a higher risk of aneurysm rupture when a circle of Willis anomaly was present (p=0.0245, OR 3.72 (CI 1.18 to 11.66)).
This series shows that circle of Willis anomalies are more commonly found in ruptured as opposed to unruptured cerebral aneurysms of the anterior and posterior communicating arteries. The presence of a circle of Willis anomaly may be an important characteristic for selecting patients for preventive aneurysm treatment.
Recanalization and angiographic reperfusion are key elements to successful endovascular and interventional acute ischemic stroke (AIS) therapy. Intravenous recombinant tissue plasminogen activator ...(rt-PA), the only established revascularization therapy approved by the US Food & Drug Administration for AIS, may be less effective for large artery occlusion. Thus, there is enthusiasm for endovascular revascularization therapies, which likely provide higher recanalization rates, and trials are ongoing to determine clinical efficacy and compare various methods. It is anticipated that clinical efficacy will be well correlated with revascularization of viable tissue in a timely manner.
Reporting, interpretation, and comparison of the various revascularization grading methods require agreement on measurement criteria, reproducibility, ease of use, and correlation with clinical outcome. These parameters were reviewed by performing a Medline literature search from 1965 to 2011. This review critically evaluates current revascularization grading systems.
The most commonly used revascularization grading methods in AIS interventional therapy trials are the thrombolysis in cerebral ischemia (TICI, pronounced "tissy") and thrombolysis in myocardial ischemia (TIMI) scores. Until further technical and imaging advances can incorporate real-time reliable perfusion studies in the angio-suite to delineate regional perfusion more accurately, the TICI grading system is the best defined and most widely used scheme. Other grading systems may be used for research and correlation purposes. A new scale that combines primary site occlusion, lesion location, and perfusion should be explored in the future.
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