Cerebrovascular disease drives Alzheimer plasma biomarker concentrations in adults with Down syndrome.

Importance: By age 40 years over 90% of adults with Down syndrome (DS) have Alzheimer's disease (AD) pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with DS have elevated cerebrovascular disease (CVD) markers that track with the clinical progression of AD, suggesting a role for CVD that is hypothesized to be mediated by inflammatory factors.

Objective: To examine the pathways through which small vessel CVD contributes to AD-related pathophysiology and neurodegeneration in adults with DS.

Impacts of host gender on Schistosoma mansoni risk in rural Uganda-A mixed-methods approach.

Background: The World Health Organization identified Uganda as one of the 10 highly endemic countries for schistosomiasis. Annual mass drug administration (MDA) with praziquantel has led to a decline in intensity of Schistosoma mansoni infections in several areas. However, as hotspots with high (re)infection rates remain, additional research on risk factors and implementing interventions to complement MDA are required to further reduce disease burden in these settings.

Imaging single DNA molecules for high precision NIPT.

Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing.

Profiling cellular protein complexes by proximity ligation with dual tag microarray readout.

Patterns of protein interactions provide important insights in basic biology, and their analysis plays an increasing role in drug development and diagnostics of disease. We have established a scalable technique to compare two biological samples for the levels of all pairwise interactions among a set of targeted protein molecules. The technique is a combination of the proximity ligation assay with readout via dual tag microarrays.

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries.

Objective: To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs.

Design: Population based cohort study using data from the national health registers.

Setting: Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007.

ProteinSeq: high-performance proteomic analyses by proximity ligation and next generation sequencing.

Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 µl of blood plasma.

Inequality in quality? Regional and educational differences in treatment with fluoroquinolone in urinary tract infection of 236,376 Swedish patients.

Background: In an international effort to reduce antibiotic resistance, in part suggested to be the effect of inappropriate antibiotic use, several quality indicators for outpatient antibiotic use have been proposed. In this study, geographical and educational differences in fluoroquinolone prescription in the treatment of urinary tract infection in women are presented.

Methods: The age-adjusted ratio of women who were dispensed fluoroquinolones (ciprofloxacin or norfloxacin) among all 236,376 women dispensed any of the following antibiotics used in the treatment of lower urinary tract infection were studied: ciprofloxacin, norfloxacin, pivmecillinam, trimethoprim and nitrofurantoin.

Targeted resequencing of candidate genes using selector probes.

Targeted genome enrichment is a powerful tool for making use of the massive throughput of novel DNA-sequencing instruments. We herein present a simple and scalable protocol for multiplex amplification of target regions based on the Selector technique. The updated version exhibits improved coverage and compatibility with next-generation-sequencing (NGS) library-construction procedures for shotgun sequencing with NGS platforms.

National surveillance of surgical-site infection through register-based analysis of antibiotic use after inguinal hernia repair.

Background: Systematic surveillance of surgical-site infections is not standard. The aim of this retrospective cohort study was to evaluate the feasibility of using existing national health registers for surveillance of postoperative antibiotic treatment suggestive of surgical-site infection.

Methods: Data from national registers on hospital admissions and drug use were combined.

Single molecule analysis of combinatorial splicing.

Alternative splicing creates diverse mRNA isoforms from single genes and thereby enhances complexity of transcript structure and of gene function. We describe a method called spliceotyping, which translates combinatorial mRNA splicing patterns along transcripts into a library of binary strings of nucleic acid tags that encode the exon composition of individual mRNA molecules. The exon inclusion pattern of each analyzed transcript is thus represented as binary data, and the abundance of different splice variants is registered by counts of individual molecules.

Sensitive plasma protein analysis by microparticle-based proximity ligation assays.

Detection of proteins released in the bloodstream from tissues damaged by disease can promote early detection of pathological conditions, differential diagnostics, and follow-up of therapy. Despite these prospects and a plethora of candidate biomarkers, efforts in recent years to establish new protein diagnostic assays have met with limited success. One important limiting factor has been the challenge of detecting proteins present at trace levels in complex bodily fluids.

Education and drug use in Sweden--a nationwide register-based study.

Purpose: To analyse educational variations in prescriptions dispensed in Sweden. A better knowledge of the use of drugs in the population, including socioeconomic distribution, is a prerequisite in efforts to estimate whether drugs are being prescribed and used according to need. This knowledge may also facilitate the identification of selection or confounding factors when analysing outcome or adverse side effects of drug treatment.

Padlock and proximity probes for in situ and array-based analyses: tools for the post-genomic era.

Highly specific high-throughput assays will be required to take full advantage of the accumulating information about the macromolecular composition of cells and tissues, in order to characterize biological systems in health and disease. We discuss the general problem of detection specificity and present the approach our group has taken, involving the reformatting of analogue biological information to digital reporter segments of genetic information via a series of DNA ligation assays. The assays enable extensive, coordinated analyses of the numbers and locations of genes, transcripts and protein.

A dual-tag microarray platform for high-performance nucleic acid and protein analyses.

DNA microarrays serve to monitor a wide range of molecular events, but emerging applications like measurements of weakly expressed genes or of proteins and their interaction patterns will require enhanced performance to improve specificity of detection and dynamic range. To further extend the utility of DNA microarray-based approaches we present a high-performance tag microarray procedure that enables probe-based analysis of as little as 100 target cDNA molecules, and with a linear dynamic range close to 10(5). Furthermore, the protocol radically decreases the risk of cross-hybridization on microarrays compared to current approaches, and it also allows for quantification by single-molecule analysis and real-time on-chip monitoring of rolling-circle amplification.

Printing protein arrays from DNA arrays.

We describe a method, DNA array to protein array (DAPA), which allows the 'printing' of replicate protein arrays directly from a DNA array template using cell-free protein synthesis. At least 20 copies of a protein array can be obtained from a single DNA array. DAPA eliminates the need for separate protein expression, purification and spotting, and also overcomes the problem of long-term functional storage of surface-bound proteins.

Equal access to treatment? Population-based follow-up of drugs dispensed to patients after acute myocardial infarction in Sweden.

Background And Objective: The establishment of national guidelines is one approach to creating equity in terms of access to care, and both internationally and in Sweden, guidelines have been developed for coronary heart disease. We have analysed drug treatment in Sweden according to national guidelines after acute myocardial infarction (AMI). The aim was to investigate whether there are differences between population groups according to sex, education, country of birth and diabetes.

Microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes.

The World Organization for Animal Health (Office International des Epizooties, OIE) includes the diseases caused by foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV), as "Diseases Notifiable to the OIE". Foot-and-mouth disease (FMD) outbreaks have severe economical as well as social effects and cannot be differentiated from the diseases caused by the other two viruses on the basis of clinical symptoms. Efficient laboratory techniques are therefore required for detection and identification of the viruses causing similar vesicular symptoms in swine.

Common problems with antiretroviral therapy among three Swedish groups of HIV infected individuals.

Objective: The main objective of this study was to identify and compare the common problems and difficulties associated with combination antiretroviral therapy (CART) as experienced by three major groups of HIV infected individuals (homo- or bisexuals, former injecting drug users and origins of Sub-Saharan Africa) in Sweden.

Methods: Based on the results from in-depth interviews with 15 representatives from the three major groups, a questionnaire was designed for use in a problem detection study (PDS). The study was conducted with 195 HIV-positive patients residing in the major cities of Sweden.

Pharmacy care perspectives on problems with HIV antiretroviral therapy in Sweden.

Objective: This study has three main objectives (1) to identify the major problems or difficulties pharmacy staff in Sweden experience regarding pharmacy care of patients receiving antiretroviral therapy, (2) to identify the perceptions of pharmacy staff regarding what are patient-related concerns with antiretroviral therapy and (3) to compare the extent to which pharmacy staff awareness matches patient perceptions regarding what are the major problems or difficulties associated with antiretroviral therapy.

Methods: A problem detection study (PDS) containing two questionnaires was conducted: one to be completed by pharmacy staff and another to be completed by both pharmacy staff and patients. In the latter survey, staff were asked about what they thought that patients would have responded.

Sensitive protein detection via triple-binder proximity ligation assays.

The detection of weakly expressed proteins and protein complexes in biological samples represents a fundamental challenge. We have developed a new proximity-ligation strategy named 3PLA that uses three recognition events for the highly specific and sensitive detection of as little as a hundred molecules of the vascular endothelial growth factor (VEGF), the biomarkers troponin I, and prostate-specific antigen (PSA) alone or in complex with an inhibitor--demonstrating the versatility of 3PLA.

Existence of antimalarial formulations with low bioavailability in Tanzania.

The main objective of this work was to assess the relative bioavailability of two tablet formulations containing sulfadoxine/pyrimethamine (SP) and marketed in Tanzania. Twelve healthy volunteers were randomized to receive a single oral dose of three SP tablets each containing 500 mg sulfadoxine (SDX) and 25 mg pyrimethamine (PYR) in a form of either A (a locally manufactured SP tablet formulation, manufactured by a local pharmaceutical industry in Tanzania) or B (Fansidar), Hoffmann La Roche, Basel, Switzerland, an innovator's SP) after an overnight fasting. Serial blood samples (100 microL) were collected from a finger prick in duplicate up to 10 days and dried on Whatman filter paper.