A Colorimetric Biosensing Platform with Aptamers, Rolling Circle Amplification and Urease-Mediated Litmus Test.

Here we report on an ultra-sensitive colorimetric sensing platform that takes advantage of both the strong amplification power of rolling circle amplification (RCA) and the high efficiency of a simple urease-mediated litmus test. The presence of a target triggers the RCA reaction, and urease-labelled DNA can hybridize to the biotinylated RCA products and be immobilized onto streptavidin-coated magnetic beads. The urease-laden beads are then used to hydrolyze urea, leading to an increase in pH that can be detected by a simple litmus test. We show this sensing platform can be easily integrated with aptamers for sensing diverse targets via the detection of human thrombin and platelet-derived growth factor (PDGF) utilizing structure-switching aptamers as well as SARS-CoV-2 in human saliva using a spike-binding trimeric DNA aptamer. Furthermore, we demonstrate that this colorimetric sensing platform can be integrated into a simple paper-based device for sensing applications.

No silver bullet? Snow leopard prey selection in Mt. Kangchenjunga, Nepal.

In this study, we investigated the impact of domestic and wild prey availability on snow leopard prey preference in the Kangchenjunga Conservation Area of eastern Nepal-a region where small domestic livestock are absent and small wild ungulate prey are present. We took a comprehensive approach that combined fecal genetic sampling, macro- and microscopic analyses of snow leopard diets, and direct observation of blue sheep and livestock in the KCA. Out of the collected 88 putative snow leopard scat samples from 140 transects (290 km) in 27 (4 × 4 km2) sampling grid cells, 73 (83%) were confirmed to be from snow leopard. The genetic analysis accounted for 19 individual snow leopards (10 males and 9 females), with a mean population size estimate of 24 (95% CI: 19-29) and an average density of 3.9 snow leopards/100 km2 within 609 km2. The total available prey biomass of blue sheep and yak was estimated at 355,236 kg (505 kg yak/km2 and 78 kg blue sheep/km2). From the available prey biomass, we estimated snow leopards consumed 7% annually, which comprised wild prey (49%), domestic livestock (45%), and 6% unidentified items. The estimated 47,736 kg blue sheep biomass gives a snow leopard-to-blue sheep ratio of 1:59 on a weight basis. The high preference of snow leopard to domestic livestock appears to be influenced by a much smaller available biomass of wild prey than in other regions of Nepal (e.g., 78 kg/km2 in the KCA compared with a range of 200-300 kg/km2 in other regions of Nepal). Along with livestock insurance scheme improvement, there needs to be a focus on improved livestock guarding, predator-proof corrals as well as engaging and educating local people to be citizen scientists on the importance of snow leopard conservation, involving them in long-term monitoring programs and promotion of ecotourism.

Gaps of care in patients with venous thrombotic embolism: a qualitative study.

BACKGROUND: Venous thromboembolism (VTE) includes pulmonary embolism (PE) and deep vein thrombosis (DVT), and results in 100,000 deaths annually in the United States. There is low global VTE awareness, including limited data regarding difficulties patients encounter during their management. This study aims to identify a patient's perspective on VTE gaps of care. METHODS: This is a qualitative study using semi-structured interviews with VTE patients, who had been previously diagnosed and treated for at least one VTE event in their lifetime. Participants were separated in five focused groups; sample size was defined by data saturation. Interviews were audio recorded, transcribed verbatim, and analyzed thematically using framework analysis based on data saturation evaluation. The study was approved by a local institutional review board. We used inductive framework analysis to interpret the data. RESULTS: Twenty participants were included in the analysis. Ten participants (50%) were men. Three major themes were identified: 1) concerned about limited disease knowledge; 2) VTE awareness in healthcare system; 3) incomplete communication during transitional and follow-up care. CONCLUSIONS: Findings suggest that gaps of VTE care extend in different levels of the medical system, including: the patient, physicians, and medical teams. Patients were sensitive to a lack of disease awareness among healthcare providers. There was appreciation for subspecialty care recommended for VTE. In a qualitative study, using the patient perspective, we have detected frustrations and perceived areas of improvement of the care of the patient with VTE. These gaps are anchored in perceived lack of disease awareness and difficult transitional care.

Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.

BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.

Early exposure to antibiotics and infections and the incidence of atopic eczema: a population-based cohort study.

It has been suggested that infants exposed to antibiotics are at increased risk for atopic eczema (AE), whereas the early exposure to infections might be protective. This study describes the complex relationship between early exposure to infections, anti-infectious treatment with antibiotics, and incident AE. Using a German population-based administrative health-care and prescription database, we established a cohort of 370 children not diagnosed as having AE during their first year of life. For each individual child we identified all infections and prescriptions of antibiotics within the first year as well as incident AE within the second year of life. Crude analyses suggested that early infections and exposure to antibiotics are risk factors for AE. However, stratified analyses indicated that early infections were only associated with a higher rate of AE when treated with broad-spectrum antibiotics such as cephalosporines or macrolides. The risk ratio (RR) of children with early respiratory tract infections not treated with antibiotics was 0.69 [95% confidence interval (95% CI) 0.39 to 1.24], whereas respiratory tract infections treated with macrolides (RR: 2.15, 95% CI: 1.18-3.91) or cephalosporines (RR: 1.93, 95% CI: 1.07-3.49) significantly increased the risk for AE. The results for other common childhood infections tended to be similar. Antibiotic treatment appears to modify the association between early infections and subsequent AE. We found no evidence that infections per se significantly alter the likelihood for subsequent AE.

The role of physical activity in the prevention of osteoporosis in postmenopausal women-An update.

CONTEXT AND OBJECTIVE: Osteoporosis causes an increase in bone fragility. Its clinical significance mainly refers to (hip) fractures secondary to (low or moderate) trauma. In Europe and North America about 6% of men and 21% of women aged 50-84 years are classified to have osteoporosis. Although it is well accepted that exercise is essential for the management of osteoporosis, the exact role of physical activity in the primary and secondary prevention of osteoporotic fractures is still controversial. METHODS: The MEDLINE database and reference lists of selected publications were systematically searched for randomized controlled trials and prospective cohort studies, respectively, published since January 2000 regarding the association of physical activity and osteoporosis in postmenopausal women. RESULTS: Two prospective cohort studies indicate the clinical relevance of this association by showing an inverse relationship between physical activity and the risk of hip fracture. There is convincing evidence that physical activity effectively slows bone loss in postmenopausal women in a dose-dependent manner. Exercise programs may increase bone mineral density. CONCLUSION: In order to maximize the goals of public health most effective, individually adapted, intense, high impact exercise programs are needed. However, they may be complicated to communicate and adherence on the population level may be hard to achieve. These programs must be weighed against popular and applicable existing programs (e.g. aerobic classes, Tai Chi, and walking) which appear to be easier to adhere to but appear to be less effective in the prevention of osteoporotic fractures in the individual postmenopausal women.

Outpatient care and medical treatment of children and adults with atopic eczema.

BACKGROUND: Despite the high prevalence, morbidity and economic burden of atopic eczema (AE), data on outpatient care of affected patients are missing. METHODS: Utilizing a population-based administrative health care database from Saxony, Germany, this study describes outpatient care and medical treatment of AE by different medical disciplines in 2003 and 2004 by means of a representative sample of 11,555 patients with AE. RESULTS: About 60% of all patients with AE seeking outpatient care were adults. Of the adults 66% and among children 51% consulted a dermatologist at least once within the study period. More than 50% of patients in all age groups received potent topical steroids. Of all patients 8% and 3% received topical pimecrolimus and topical tacrolimus, respectively. More than 10% of patients received systemic steroids, while less than 0.1% was given cyclosporine. The mean annual amount of topical anti-inflammatory treatment per patient was about 40 grams. CONCLUSIONS: Unexpectedly high proportions of patients with AE received potent topical and systemic steroids. The average total amount of prescribed medications was low. This study suggests insufficient care and medical treatment of patients with AE in routine practice.

Systemic treatment of severe atopic eczema: a systematic review.

Systemic immunosuppressive agents are recommended for patients with atopic eczema in whom disease activity cannot be controlled adequately with topical treatments. Guidelines do not give clear advice which agents to prefer. We systematically reviewed clinical trials on systemic treatment for severe atopic eczema to provide evidence-based treatment recommendations. Standardized literature search, independent standardized assessment of eligibility and data abstraction was performed by 2 reviewers. Twenty-seven studies totalling 979 patients were included. Eleven studies consistently showed effectiveness of cyclosporine. Cyclosporine is recommended as first option for patients with atopic eczema refractory to conventional treatment. Evidence from randomized controlled trials also exists for interferon-? and azathioprine. Although frequently used in clinical practice, systemic glucocorticosteroids have not been assessed adequately in studies. Mycophenolate mofetile showed effectiveness in 2 small uncontrolled studies. Intravenous immunoglobulins and infliximab are not recommended based on published data.