Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Cost-effectiveness of tiotropium versus usual care and glycopyrronium in the treatment of chronic obstructive pulmonary disease in Sweden

BACKGROUND: Tiotropium (TIO) is a well-established bronchodilator, LAMA (long-acting anticholinergic), for the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). Clinical evidence suggests that tiotropium is superior to usual non-LAMA care (UC) but may also have benefits compared to other LAMAs in preventing and limiting the effects of severe exacerbations. The primary objective of this study was to undertake a cost-effectiveness analysis of adding tiotropium to usual care versus usual care alone. A secondary objective was to assess the cost-effectiveness of tiotropium compared to glycopyrronium (GLY), another LAMA. The study was conducted with a Swedish setting in mind. METHODS: A Markov cohort model, incorporating the effects of exacerbations, was populated with efficacy data from the UPLIFT and SPARK trials and epidemiological data relevant for a Swedish patient population. Treatment efficacy of tiotropium was modelled as a lowering of the risk of exacerbations and as a slow-down of overall disease progression. The model followed patients over their remaining life-time. RESULTS: The base case analysis showed that patients treated with tiotropium gained 0.07 quality-adjusted life years (QALYs) compared to usual care alone at an incremental cost of SEK 15,041, resulting in a cost per QALY gained of SEK 224,850. Compared to glycopyrronium the QALY gained was estimated to 0.23 QALYs in favour of tiotropium at an incremental cost of SEK 2423, yielding a cost per QALY gained of SEK 10,456. The results were mainly driven by differences in the risk of severe exacerbations. CONCLUSION: At the current implicit willingness-to-pay (WTP) per QALY threshold in Sweden, the results from this study indicate that tiotropium is a highly cost-effective intervention when added to usual non-LAMA care in the treatment of moderate to very severe COPD in Sweden. In addition, tiotropium is a highly cost-effective intervention when compared to glycopyrronium monotherapy

Detection and follow-up of chronic obstructive pulmonary disease (COPD) and risk factors in the Southern Cone of Latin America. the pulmonary risk in South America (PRISA) study

<p>Abstract</p> <p>Background</p> <p>The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition.</p> <p>Methods/Design</p> <p>PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken.</p> <p>Discussion</p> <p>There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary disease, patient characteristics and changes in lung function over time as well as quality of life and health care resource utilization. Information gathered during the PRISA Study will inform public health interventions and prevention practices to reduce risk of COPD in the region.</p

Effectiveness of a physical activity program on cardiovascular disease risk in adult primary health-care users: the “Pas-a-Pas” community intervention trial

Abstract Background Physical activity is a major, modifiable, risk factor for cardiovascular disease (CVD) that contributes to the prevention and management of CVD. The aim of this study was to assess the short- and medium-term effectiveness of 9 months of a supervised physical activity program, including sociocultural activities, on CVD risk in adults. Methods Multicentered, randomized, controlled community intervention involving 364 patients in four primary care centers. The participants were randomly assigned to a Control Group (CG = 104) or Intervention Group (IG = 260); mean age 65.19 years; 76.8% women. The intervention consisted of 120 min/week walking (396 METs/min/week) and sociocultural gathering once a month. Clinical history, physical activity, dietary intake, CVD risk factors (smoking, systolic and diastolic blood pressure, weight, waist circumference, BMI, total cholesterol, LDL- and HDL-cholesterol, triglycerides, glycosylated hemoglobin and glucose) and global CVD risk were assessed at baseline and at the end of the intervention and multivariate models were applied to the data. Incidence of adverse cardiovascular events and continued adherence to the physical activity were assessed 2 years after intervention. Results At the end of the intervention period, in the IG relative to the CG group, there was a significant increase in physical activity (774.81 METs/min/week), a significant change during the intervention period in systolic blood pressure (−6.63 mmHg), total cholesterol (−10.12 mg/dL) and LDL-cholesterol (−9.05 mg/dL) even after adjustment for potential confounders. At 2 years after the intervention, in the IG, compared with the CG, tthe incidence of adverse cardiovascular events was significantly lower (2.5% vs. 10.5%) and the adherence to regular physical activity was higher (72.8% vs 27.2%) in IG compared to CG. Conclusions This community-based physical activity program improved cardiovascular health in the short- as well as medium-term, and promoted regular physical activity in the medium-term in older Spanish adults. Trials registration Clinicaltrials.gov ID NCT02767739 . Trial registered on May 5th, 2016. Retrospectively registere

Impact of patient characteristics, education and knowledge on emergency room visits in patients with asthma and COPD: a descriptive and correlative study

<p>Abstract</p> <p>Background</p> <p>Asthma and COPD are major health problems and an extensive burden for the patient and the health care system. Patient education has been recommended, but the influence on knowledge and health outcomes is not fully examined. Our aims were to compare patient characteristics, education and knowledge in patients who had an emergency room (ER) visit, to explore factors related to disease knowledge, and to investigate patient characteristics, patient education and knowledge in relation to further ER visits over a 12 month period.</p> <p>Methods</p> <p>Eighty-four patients with asthma and 52 with COPD, who had had an ER visit, were included. They were interviewed by telephone 4 to 6 weeks after the ER visit and followed for a year.</p> <p>Results</p> <p>Patients with COPD were older, more sedentary, had had more ER visits the previous year, and had more co morbidity than patients with asthma. About 80% of the patients had received information from health professionals or participated in education/rehabilitation, but a minority (< 20%) reported that their knowledge about how to handle the disease was good. Patients with "good knowledge" were younger, were more likely to have asthma diagnose, and had a higher educational background (p < 0.05). Sixty-seven percent of the patients with COPD had repeated ER visits during the following year versus 42% in asthma (p < 0.05) (adjusted HRR: 1.73 (1.03-2.90)). Patients who had had ER visits the year before inclusion had a higher risk of ER visits the following year (adjusted HRR: 3.83 (1.99-7.38)). There were no significant differences regarding patient education and knowledge between the group with and without further ER visits after adjusting for sex, diagnose, age, and educational background.</p> <p>Conclusion</p> <p>Patients with asthma had a better self reported knowledge of disease management and were less likely to have new exacerbations than patients with COPD. Reported level of knowledge was, however, in it self not a predictor of exacerbations. This indicates that information is not sufficient to reduce the burden of disease. Patient education focused on self-management and behavioral change should be emphasized.</p

Cellular senescence in naevi and immortalisation in melanoma: a role for p16?

Cellular senescence, the irreversible proliferative arrest seen in somatic cells after a limited number of divisions, is considered a crucial barrier to cancer, but direct evidence for this in vivo was lacking until recently. The best-known form of human cell senescence is attributed to telomere shortening and a DNA-damage response through p53 and p21. There is also a more rapid form of senescence, dependent on the p16-retinoblastoma pathway. p16 (CDKN2A) is a known melanoma susceptibility gene. Here, we use retrovirally mediated gene transfer to confirm that the normal form of senescence in cultured human melanocytes involves p16, since disruption of the p16/retinoblastoma pathway is required as well as telomerase activation for immortalisation. Expression (immunostaining) patterns of senescence mediators and markers in melanocytic lesions provide strong evidence that cell senescence occurs in benign melanocytic naevi (moles) in vivo and does not involve p53 or p21 upregulation, although p16 is widely expressed. In comparison, dysplastic naevi and early (radial growth-phase, RGP) melanomas show less p16 and some p53 and p21 immunostaining. All RGP melanomas expressed p21, suggesting areas of p53-mediated senescence, while most areas of advanced (vertical growth-phase) melanomas lacked both p16 and p21, implying escape from both forms of senescence (immortalisation). Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi. We conclude that cell senescence can form a barrier to melanoma development. This also provides a potential explanation of why p16 is a melanoma suppressor gene

Successful Expansion but Not Complete Restriction of Tropism of Adeno-Associated Virus by In Vivo Biopanning of Random Virus Display Peptide Libraries

Targeting viral vectors to certain tissues in vivo has been a major challenge in gene therapy. Cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids in vitro but so far this system could not easily be translated to in vivo applications. Using a novel, PCR-based amplification protocol for peptide libraries displayed on adeno-associated virus (AAV), we selected vectors for optimized transduction of primary tumor cells in vitro. However, these vectors were not suitable for transduction of the same target cells under in vivo conditions. We therefore performed selections of AAV peptide libraries in vivo in living animals after intravenous administration using tumor and lung tissue as prototype targets. Analysis of peptide sequences of AAV clones after several rounds of selection yielded distinct sequence motifs for both tissues. The selected clones indeed conferred gene expression in the target tissue while gene expression was undetectable in animals injected with control vectors. However, all of the vectors selected for tumor transduction also transduced heart tissue and the vectors selected for lung transduction also transduced a number of other tissues, particularly and invariably the heart. This suggests that modification of the heparin binding motif by target-binding peptide insertion is necessary but not sufficient to achieve tissue-specific transgene expression. While the approach presented here does not yield vectors whose expression is confined to one target tissue, it is a useful tool for in vivo tissue transduction when expression in tissues other than the primary target is uncritical

ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers

In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression

Prevalence of chronic kidney disease in South Asia: a systematic review

Background: Chronic kidney disease (CKD) is becoming a major public health problem around the world. But the prevalence has not been reported in South Asian region as a whole. This study aimed to systematically review the existing data from population based studies in this region to bridge this gap. Methods Articles published and reported prevalence of CKD according to K/DOQI practice guideline in eight South Asian countries between December 1955 and April 2017 were searched, screened and evaluated from seven electronic databases using the PRISMA checklist. CKD was defined as creatinine clearance (CrCl) or GFR less than 60 ml/min/1.73 m2. Results Sixteen population-based studies were found from four South Asian countries (India, Bangladesh, Pakistan and Nepal) that used eGFR to measure CKD. No study was available from Sri Lanka, Maldives, Bhutan and Afghanistan. Number of participants ranged from 301 in Pakistan to 12,271 in India. Majority of the studies focused solely on urban population. Different studies used different equations for measuring eGFR. The prevalence of CKD ranged from 10.6% in Nepal to 23.3% in Pakistan using MDRD equation. This prevalence was higher among older age group people. Equal number of studies reported high prevalence among male and female each. Conclusions This systematic review reported high prevalence of CKD in South Asian countries. The findings of this study will help pertinent stakeholders to prepare suitable policy and effective public health intervention in order to reduce the burden of this deadly disease in the most densely populated share of the globe