In healthy older subjects, the glycaemic response to carbohydrate-containing meals is dependent on gastric emptying and intestinal absorption; when the latter is slowed, the magnitude of the rise in ...glucose is attenuated. The oligosaccharide α-cyclodextrin has been reported to diminish the glycaemic response to starch in young adults; this effect has been attributed to the inhibition of pancreatic amylase. We examined the effects of α-cyclodextrin on gastric emptying of, and the glycaemic and insulinaemic responses to, oral sucrose in healthy older subjects; as sucrose is hydrolysed by intestinal disaccharides, any effect(s) of α-cyclodextrin would not be attributable to amylase inhibition. A total of ten subjects (seven males and three females, age 68–76 years) were studied on 2 d. Gastric emptying, blood glucose and serum insulin were measured after ingestion of a 300 ml drink containing 100 g sucrose, labelled with 99mTc-sulphur colloid, with or without 10 g α-cyclodextrin. Gastric emptying was slowed slightly by α-cyclodextrin; this effect was evident between 135 and 195 min and was associated with a slight increase (P < 0·05) in distal stomach retention. After α-cyclodextrin, blood glucose was slightly less (P < 0·05) at 60 min, and serum insulin was less (P < 0·0005) at 90 and 120 min. There was no difference in the incremental areas under the curve (iAUC) for blood glucose, but there was a trend for the iAUC for serum insulin to be lower (P = 0·09) after α-cyclodextrin. We conclude that in a dose of 10 g, α-cyclodextrin has modest effects to slow gastric emptying of, and modify the glycaemic and insulinaemic responses to, oral sucrose, probably due to delayed intestinal carbohydrate absorption.
AstraZeneca (the manufacturer of Diprivan) presents its review of the history of the so-called 'propofol infusion syndrome', highlighting the difficulties in analysing the incomplete information ...available. Theories as to its causality are presented and discussed; these include mitochondrial toxicity, mitochondrial defects, impaired tissue oxygenation and carbohydrate deficiency. A review of published and confidential safety data is presented and discussed; it concludes that the major risk factors for its development appear to be poor oxygen delivery, sepsis, serious cerebral injury and high propofol dosage. In some reports an increasing lipaemia was noted and was likely to be due to a failure of hepatic lipid regulation, possibly related to poor oxygenation and/or possibly a lack of glucose. In some cases an increasing lipaemia was the first indication of impending 'propofol infusion syndrome' onset and it should not be viewed as a benign sign. The lipaemia can lead to sequestration of propofol into the lipid phase, leading to lowered free propofol levels and apparent insensitivity to propofol. In conclusion AstraZeneca advocates good haemodynamic and oxygen delivery management, adequate glucose provision, adherence to recommended propofol dosing regimes together with active management of lipaemias to both prevent and treat 'propofol infusion syndrome'.
Small genes (<150 nucleotides) have been systematically overlooked in phage genomes. We employ a large-scale comparative genomics approach to predict >40,000 small-gene families in ∼2.3 million phage ...genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions.
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•More than 40,000 small gene families predicted in phages from diverse environments•More than 5,000 small gene families predicted to encode anti-CRISPR proteins•More than 9,000 small gene families predicted to encode secreted or transmembrane proteins•Identified novel core phage proteins like baseplate proteins and phage tail proteins
Fremin et al. use comparative genomics to predict more than 40,000 small-gene families in phage from diverse environments. Small genes are approximately 3-fold more prevalent in phage than prokaryotic genomes. This resource includes more than 5,000 anti-CRISPR small-gene families and more than 9,000 secreted or transmembrane small-gene families.
This innovative book provides a dynamic--and often surprising--view of the range of environmental issues facing the United States today. A distinguished group of scholars examines the growing ...temporal, spatial, and thematic breadth of topics historical geographers are now exploring. Seventeen original chapters examine topics such as forest conservation, mining landscapes, urban environment justice, solid waste, exotic species, environmental photography, national and state park management, recreation and tourism, and pest control. Commemorating the twenty-fifth anniversary of the publication of the seminal work The American Environment: Interpretations of Past Geographies, the book clearly shows much has changed since 1992. Indeed, not only has the range of issues expanded, but an increasing number of geographers are forging links with environmental historians, promoting a level of intellectual cross-fertilization that benefits both disciplines. As a result, environmental historical geographies today are richer and more diverse than ever. The American Environment Revisited offers a comprehensive overview that gives both specialist and general readers a fascinating look at our changing relationships with nature over time.
Cell adhesion: a new target for therapy Buckley, Christopher D.; Simmons, David L.
Molecular medicine today (Regul. ed.),
10/1997, Letnik:
3, Številka:
10
Journal Article
Intercellular adhesive events are involved in a wide range of biological processes, including pattern formation and morphogenesis during development, immune responses, leukocyte recirculation, wound ...repair, tumour growth and metastasis. In the multicellular state, signals from cell adhesion molecules, along with those from growth factor and cytokine receptors, provide a range of information to the cell that is integrated to yield a final message, perhaps to maintain the cell cycle (if it is a stem cell) or follow a path towards terminal differentiation. Aberrant cell adhesion plays a key role in many developmental defects, acute and chronic inflammatory disease and cancer.
Objective Endoluminal treatment of symptomatic varicose veins (VV) reduces or eliminates inpatient hospital stays, lowers complication rates, and increases revenue for vein care centers adopting the ...technique. This study compares the outcomes and economics of two treatments for VV. Methods Since May 2007, endovenous radiofrequency ablation (RFA) of symptomatic VV has been performed at our institution. For outcome measurements, a cohort of 100 RFA procedures (26% CEAP class C5 and C6) was compared with 100 open greater or lesser saphenous stripping and ligation procedures (SL, 18% C5 and C6). Procedures were performed between August 2002 and October 2007. The time frame was chosen to allow for a 6-mo follow-up. Patients who had adjunctive removal of secondary varicosities were included in both cohorts. Cost estimates are based on the actual total direct costs derived from the hospital’s charge sheets for 20 of the 100 patients in each of the cohorts ( n = 40). The actual direct costs are based on 2009-dollar values and do not include the surgeons’ professional fees. Results Seventy-nine percent of the RFA therapies were performed in an outpatient clinic treatment room with the remaining 21% performed in an operating room (OR). For the SL group, all procedures were performed in the OR with 68% of patients requiring at least one night of hospital stay (average length of stay 1.2 d). The estimated direct cost of performing RFA in the treatment room was $906. This was considerably less than the estimated $4241 total direct cost for open SL followed by in-hospital observation. Outpatient open SL cost $2622, which is only slightly more than the $2533 cost for outpatient RFA performed in the OR. The use of RFA was associated with an earlier return to normal leisure activities (3.3 d versus 26 d, P < 0.05), fewer total hospital nights (3 d versus 82 d, P < 0.05), and less use of general anesthesia (16% versus 95%, P < 0.05). There were no major complications in the RFA group compared with three major complications in the SL group. Conclusions With the introduction of endovenous techniques at our institution, there has been a significant increase in the volume of patients seeking this less invasive treatment modality. This is due largely to the ease and comfort with which patients can now be treated as well as the reduced length of stay, reduction of general anesthetic use, and the speed at which they can return to normal activities. We recommend endovenous ablation techniques as both cost-saving and patient-preferred.
Common variable immunodeficiency (CVID) is increasingly recognized for its association with autoimmune and inflammatory complications. Despite recent advances in immunophenotypic and genetic ...discovery, clinical care of CVID remains limited by our inability to accurately model risk for non-infectious disease development. Herein, we demonstrate the utility of unbiased network clustering as a novel method to analyze inter-relationships between non-infectious disease outcomes in CVID using databases at the United States Immunodeficiency Network (USIDNET), the centralized immunodeficiency registry of the United States, and Partners, a tertiary care network in Boston, MA, USA, with a shared electronic medical record amenable to natural language processing. Immunophenotypes were comparable in terms of native antibody deficiencies, low titer response to pneumococcus, and B cell maturation arrest. However, recorded non-infectious disease outcomes were more substantial in the Partners cohort across the spectrum of lymphoproliferation, cytopenias, autoimmunity, atopy, and malignancy. Using unbiased network clustering to analyze 34 non-infectious disease outcomes in the Partners cohort, we further identified unique patterns of lymphoproliferative (two clusters), autoimmune (two clusters), and atopic (one cluster) disease that were defined as CVID non-infectious endotypes according to discrete and non-overlapping immunophenotypes. Markers were both previously described {high serum IgE in the atopic cluster odds ratio (OR) 6.5 and low class-switched memory B cells in the total lymphoproliferative cluster (OR 9.2)} and novel low serum C3 in the total lymphoproliferative cluster (OR 5.1). Mortality risk in the Partners cohort was significantly associated with individual non-infectious disease outcomes as well as lymphoproliferative cluster 2, specifically (OR 5.9). In contrast, unbiased network clustering failed to associate known comorbidities in the adult USIDNET cohort. Together, these data suggest that unbiased network clustering can be used in CVID to redefine non-infectious disease inter-relationships; however, applicability may be limited to datasets well annotated through mechanisms such as natural language processing. The lymphoproliferative, autoimmune, and atopic Partners CVID endotypes herein described can be used moving forward to streamline genetic and biomarker discovery and to facilitate early screening and intervention in CVID patients at highest risk for autoimmune and inflammatory progression.
Abstract
Background
Determining the presence of amyloid pathology
in vivo
is possible by visual read (VR) and quantification. VR is the method of reference for clinically assessing amyloid pathology, ...and guidelines are based on distinguishing positive scans from Alzheimer’s dementia patients from healthy controls negative scans. More quantitative approaches using cut‐off values also focused on identification of early amyloid pathology in preclinical populations. This study investigated whether a VR‐defined cut‐off would perform similarly to recently proposed Centiloid (CL) cut‐offs.
Methods
18
Fflutemetamol PET images of 352 cognitively unimpaired (CU) participants from the ALFA+ and 145 patients from the ADC cohort were included (Table 1). Scans were read by an experienced reader according to the product guidelines, collecting the number of positive regions (0‐5) and the final positive/negative classification. Tracer uptake was quantified with the standard CL pipeline. Using VR as the reference standard, previously proposed CL=12/30 cut‐offs were tested for sensitivity and specificity. In addition, a data‐driven cut‐off was determined using ROC analysis and the Youden Index.
Results
152 (30.6%) scans were read as positive. The CL=30 cut‐off resulted in 80.3% sensitivity and 100% specificity, while the CL=12 cut‐off greatly improved the sensitivity to 95.2% and kept a high specificity at 95.9%. Based on the ROC analysis, a CL=16 cut‐off was found, with both excellent sensitivity (93.9%) and specificity (98.2%) (AUC of .99, 95% CI: .989‐.998) (Figure 1). Mean CL values significantly increased with increasing number of visually positive regions (
F
=568.10,
η
2
=.85,
p
<.01, Figure 2, Table 2). Number of visually positive regions was related to age in the ALFA+ CU population (
F
=9.17,
η
2
=.12,
p
<.01).
Conclusion
Using VR as reference standard, we found a similar CL cut‐off to that proposed by previous work using independent amyloid biomarkers (post‐mortem and CSF). These results illustrate that CL can be
as sensitive as
VR to early amyloid pathology. Importantly, these results could (at least partially) be attributed the level of experience of the reader and the inclusion of mainly cognitively unimpaired subjects. In addition, our results suggests that it can be of value to visually capture the extent of amyloid burden in addition to negative/positive classifications.
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