Abstract Background/Objective Familial Hypercholesterolaemia (FH) is caused by mutations in genes of the Low Density Lipoprotein (LDL) receptor pathway. A definitive diagnosis of FH can be made by ...the demonstration of a pathogenic mutation. The Wales FH service has developed scoring criteria to guide selection of patients for DNA testing, for those referred to clinics with hypercholesterolaemia. The criteria are based on a modification of the Dutch Lipid Clinic scoring criteria and utilise a combination of lipid values, physical signs, personal and family history of premature cardiovascular disease. They are intended to provide clinical guidance and enable resources to be targeted in a cost effective manner. Methods 623 patients who presented to lipid clinics across Wales had DNA testing following application of these criteria. Results The proportion of patients with a pathogenic mutation ranged from 4% in those scoring 5 or less up to 85% in those scoring 15 or more. LDL-cholesterol was the strongest discriminatory factor. Scores gained from physical signs, family history, coronary heart disease, and triglycerides also showed a gradient in mutation pick-up rate according to the score. Conclusion These criteria provide a useful tool to guide selection of patients for DNA testing when applied by health professionals who have clinical experience of FH.
Abstract
As important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re‐emerging infectious diseases. The most ...devastating of the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the
O
ld and
N
ew
W
orld. Here we present the first global transcriptome analysis of the
O
ld
W
orld vector of cutaneous leishmaniasis,
P
hlebotomus papatasi
(
S
copoli) and compare this transcriptome to that of the
N
ew
W
orld vector of visceral leishmaniasis,
L
utzomyia longipalpis
. A normalized
cDNA
library was constructed using pooled
mRNA
from
P
hlebotomus papatasi
larvae, pupae, adult males and females fed sugar, blood, or blood infected with
Leishmania major
. A total of 47 615 generated sequences was cleaned and assembled into 17 120 unique transcripts. Of the assembled sequences, 50% (8837 sequences) were classified using
G
ene
O
ntology (
GO
) terms. This collection of transcripts is comprehensive, as demonstrated by the high number of different
GO
categories. An in‐depth analysis revealed 245 sequences with putative homology to proteins involved in blood and sugar digestion, immune response and peritrophic matrix formation. Twelve of the novel genes, including one trypsin, two peptidoglycan recognition proteins (
PGRP
) and nine chymotrypsins, have a higher expression level during larval stages. Two novel chymotrypsins and one novel
PGRP
are abundantly expressed upon blood feeding. This study will greatly improve the available genomic resources for
P
. papatasi
and will provide essential information for annotation of the full genome.
Mucinous ductal ectasia of the pancreas McDowell, R K; Gazelle, G S; Murphy, B L ...
Journal of computer assisted tomography,
05/1997, Letnik:
21, Številka:
3
Journal Article
Recenzirano
Pancreatic mucinous ductal ectasia (MDE) is a recently described and poorly understood disorder, with few cases reported in the imaging literature. We undertook this study to describe the spectrum of ...CT and pancreatographic findings of MDE and to investigate the incidence of associated pancreatic malignancy.
The medical records, CT scans, and pancreatograms of 12 consecutive patients with pathologically proven MDE were retrospectively reviewed. There were nine men and three women, ranging in age from 37 to 72 years (mean 59 years).
Focal lesions involved primarily the uncinate (two patients) and head (eight patients) by CT imaging. The entire gland was involved in two patients. CT findings were variable and included focal pancreatic enlargement, a low attenuation or cystic mass, low attenuation of the entire gland, or marked ductal dilatation. Pancreatographic findings were more consistent, showing ductal dilatation with or without intraluminal filling defects, obstruction, or displacement. In all cases, findings at endoscopy were felt to be characteristic, with ductal dilatation, filling defects, or abundant mucus seen upon cannulation of the pancreatic duct. Carcinoma-in-situ was present in six cases, cellular atypia without malignancy in two, and in three cases the lesions were histologically benign. One case demonstrated invasive adenocarcinoma. No finding or group of findings on CT or pancreatography permitted differentiation between benign and malignant lesions.
MDE can present with a variety of appearances on CT, none of which is diagnostic. Pancreatography can be diagnostic if dilatation and intraluminal filling defects are seen. Carcinoma-in-situ, invasive adenocarcinoma, or cellular atypia is present in approximately 75%, but cannot be accurately diagnosed prospectively.
Anxiety symptoms and disorders are highly prevalent and costly. Prospective studies suggest that physical activity may prevent anxiety development; however, this body of literature has not been ...reviewed comprehensively.
Studies measuring physical activity at baseline and anxiety at a designated follow-up at least 1 year later were located using MEDLINE, PsycINFO, and CINAHL Complete through June 2018.
Data were analyzed July–December 2018. Study quality was assessed using Q-Coh. Among studies of adults, a random-effects meta-analysis was conducted for crude and the most fully adjusted models for three outcomes: self-reported anxiety symptoms, a diagnosis of any anxiety disorder, and a diagnosis of generalized anxiety disorder. As there were few studies with diverse samples and outcome measures, findings were elaborated with a critical narrative review of all studies. Twenty-four studies (median follow-up, 4.75 years) of >80,000 unique individuals were included in the systematic review; thirteen were included in the meta-analyses. Six studies were assessed as low quality, nine as acceptable, and nine as good. From adjusted models, odds of elevated anxiety symptoms (OR=0.8742, 95% CI=0.7731, 0.9886, n=9), any anxiety disorder (OR=0.6626, 95% CI=0.5337, 0.8227, n=3), and generalized anxiety disorder specifically (OR=0.5438, 95% CI=0.3231, 0.9153, n=3) were significantly lower after physical activity exposure.
Available evidence suggests that engaging in physical activity protects against anxiety symptoms and disorders. However, notable challenges in the current evidence base include issues regarding exposure and outcome measures, consistent adjustment for putative confounders, representativeness of samples, and attrition bias, which warrant further research.
The radiologic evaluation of sepsis of unknown origin has changed dramatically since the introduction of cross-sectional imaging. Interventional procedures such as abscess drainage, cholecystostomy, ...biliary drainage, nephrostomy, and fluid aspiration have reduced the morbidity and mortality associated with occult sources of sepsis. This article examines some of the common etiologies and treatments of sepsis in the hospitalized patient.
The terrestrial biosphere sequesters up to a third of annual anthropogenic carbon dioxide emissions, offsetting a substantial portion of greenhouse gas forcing of the climate system. Although a ...number of factors are responsible for this terrestrial carbon sink, atmospheric nitrogen deposition contributes by enhancing tree productivity and promoting carbon storage in tree biomass. Forest soils also represent an important, but understudied carbon sink. Here, we examine the contribution of trees versus soil to total ecosystem carbon storage in a temperate forest and investigate the mechanisms by which soils accumulate carbon in response to two decades of elevated nitrogen inputs. We find that nitrogen-induced soil carbon accumulation is of equal or greater magnitude to carbon stored in trees, with the degree of response being dependent on stand type (hardwood versus pine) and level of N addition. Nitrogen enrichment resulted in a shift in organic matter chemistry and the microbial community such that unfertilized soils had a higher relative abundance of fungi and lipid, phenolic, and N-bearing compounds; whereas, N-amended plots were associated with reduced fungal biomass and activity and higher rates of lignin accumulation. We conclude that soil carbon accumulation in response to N enrichment was largely due to a suppression of organic matter decomposition rather than enhanced carbon inputs to soil via litter fall and root production.
Intensive land use, such as dairying, can impair water quality. Although many guidelines exist on how to mitigate the loss of dairy-associated contaminants from land to water through best management ...practices (BMPs), few datasets exist on the success of implementation on-farm. Five dairy-dominated catchments (from 598 to 2480 ha) in New Zealand were studied from 2001 to 2020. The first period, from 2001 to 2010, involved comprehensive “extension” advice to farmers consisting of workshops, stream water quality and flow monitoring, farm practice surveys, and identified solutions to address site-specific contaminant losses. In the second period (2011−2020), termed “post-extension”, only water quality monitoring and farm practice surveys were continued. Of the water quality contaminants (including dissolved reactive phosphorus (DRP), total phosphorus (TP), ammoniacal-nitrogen, nitrate-nitrite-nitrogen NNN, suspended sediment and E. coli), 83 % of water quality trend directions were either improving (n = 16) or showed no change (n = 9) during the extension period. Over the 20-year dataset, which included the post-extension period, 20 out of 30 contaminant-catchment combinations (67 %) were improving, but nine were degrading, dominated by NNN (n = 4), DRP (n = 2) and E. coli (n = 2). Abrupt decreases in contaminant concentrations, were correlated with on-farm practice changes mainly associated with transition from direct discharge of farm dairy shed effluent to waterways to land application, and the capture of effluent from off-paddock facilities (like stand off or feed pads). Best management practices reduced phosphorus (P) forms, E. coli and sediment concentrations. Increase in NNN concentrations was caused by transitioning from flood to spray irrigation and a commensurate increase in cow numbers and NNN leaching. These data indicate that extension advice and on-farm practice change have helped to improve overall water quality over time. Nevertheless, recent regulatory threshold values for some contaminant concentrations are not being met, meaning that more actions are required, over and above the BMPs implemented.
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•Water quality and BMP implementation was studied with (2001-2010) and without (2011-2020) extension.•During extension, 83% of water quality trends were improving or showed no change.•Over the 20-year period, including post-extension, 70 % of trends were improving or showed no change.•Abrupt decreases in contamination correlated with changes like shifting to land application of dairy shed effluent.•While extension advice helped to improve water quality, additional BMPs may be needed to meet recent regulatory thresholds.
Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating ...hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8
T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.
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