Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Brain-predicted age difference mediates the association between PROMIS sleep impairment, and self-reported pain measure in persons with knee pain

Knee pain, the most common cause of musculoskeletal pain (MSK), constitutes a severe public health burden. Its neurobiological causes, however, remain poorly understood. Among many possible causes, it has been proposed that sleep problems could lead to an increase in chronic pain symptomatology, which may be driven by central nervous system changes. In fact, we previously found that brain cortical thickness mediated the relationship between sleep qualities and pain severity in older adults with MSK. We also demonstrated a significant difference in a machine-learning-derived brain-aging biomarker between participants with low-and high-impact knee pain. Considering this, we examined whether brain aging was associated with self-reported sleep and pain measures, and whether brain aging mediated the relationship between sleep problems and knee pain. Exploratory Spearman and Pearson partial correlations, controlling for age, sex, race and study site, showed a significant association of brain aging with sleep related impairment and self-reported pain measures. Moreover, mediation analysis showed that brain aging significantly mediated the effect of sleep related impairment on clinical pain and physical symptoms. Our findings extend our prior work demonstrating advanced brain aging among individuals with chronic pain and the mediating role of brain-aging on the association between sleep and pain severity. Future longitudinal studies are needed to further understand whether the brain can be a therapeutic target to reverse the possible effect of sleep problems on chronic pain

Propiedades mecánicas de la madera de álamos de cortinas forestales de Río Negro, Patagonia, Argentina

En la provincia de Río Negro, Argentina, existen en la actualidad 6000 km de longitud lineal de cortinas cortavientos de álamo. Su función principal es la protección de cultivos frutihortícolas, pero son además un recurso forestal real y potencial. El objetivo de este trabajo es conocer algunas propiedades mecánicas de la madera estos álamos, información no existente y esencial para optimizar su aprovechamiento y maximizar su valor en diferentes usos. Se apearon 15 ejemplares de los álamos más representados en cortinas forestales (álamo chileno, conti 12 y boleana) de chacras de la localidad de Allen. De cada árbol se extrajo una troza de 1,5 m de largo desde la cual se obtuvieron probetas para ensayos de propiedades mecánicas de resistencia estática de flexión, compresión (Norma ASTM D-143), resistencia al aplastamiento (Norma ASTM D-5764-97) y dureza (Norma IRAM-9570). Por un lado, los resultados obtenidos fueron del orden de los reportados para madera de otros álamos cultivados en diferentes zonas de nuestro país, algunas de ellas habilitadas para uso estructural. Por otro lado, los valores obtenidos fueron del rango de los reportados para pino ponderosa, madera ampliamente utilizada en Patagonia en la construcción de cabreadas, estructuras portantes (tirantes, vigas, columnas, etc.) y bastidores de entramados en paneles estructurales. La madera de boleana y conti 12 presentó mayores valores de resistencia a la flexión, a la compresión y al desgaste que la del álamo chileno (MOR flexión: 66,7 Mpa, MOE flexión: 8562,15 Mpa, MOR compresión: 31,22 Mpa, MOE compresión: 8270,52 Mpa, dureza radial: 1,63 kN/cm2). La resistencia al aplastamiento no presentó variaciones significativas entre ellos (conti 12: 29,42 Mpa, boleana: 30,08 Mpa y chileno: 29,65 Mpa). Estos resultados resaltan el potencial que presenta la madera de los álamos de cortinas forestales de los valles irrigados de Río Negro para ampliar sus posibilidades de uso.In Río Negro province, Argentina, there are currently 6000 km of linear length of poplar windbreaks. Its main function is the protection of fruit and vegetable crops but they are also a real and potential forest resource. The objective of this work is to know the mechanical properties of the wood these poplars, nonexistent and essential information to optimize their use and maximize their value in different uses. Fifteen specimens of the most represented poplars in forest curtains (chileno, conti 12 and boleana) of farms in Allen were cutted. From each tree a 1.5 m long log was extracted to obtain wood for mechanical properties tests of static resistance of bending, compression (ASTM D-143), dowel bearing strenght (ASTM D-5764-97) and hardness (IRAM-9570). The results obtained were of the order of those reported for wood from other poplars grown in different areas of our country, some of them accepted for structural use. On the other hand, the values obtained were from the range of those reported for ponderosa pine, wood widely used in Patagonia in the construction, load-bearing structures (beams, columns, etc.) and frames of trusses in structural panels. The wood of boleana and conti 12 presented higher values of resistance to flexion, compression and hardness than chilean poplar (MOR flexion: 66.7 Mpa, MOE flexion: 8562.15 Mpa, MOR compression: 31.22 Mpa, MOE compression: 8270.52 MPa, radial hardness: 1.63 kN / cm2). The dowel bearing strenght did not show significant variations among them (conti 12: 29.42 MPa, boleana: 30.08 MPa and chilean: 29.65 MPa). These conclusions highlight the potential of poplar wood from Río Negro forest windbreaks to expand their possibilities of use.Fil: Medina, A.A. Universidad Nacional del Comahue, Asentamiento Universitario San Martín de los Andes; ArgentinaFil: Manzione, Pablo. Universidad Nacional del Comahue. Facultad de Ingeniería. Departamento de Mecánica Aplicada. Grupo de Estudio de Polímeros Sintéticos y Naturales; ArgentinaFil: Baucis, Agustín. Universidad Nacional del Comahue, Asentamiento Universitario San Martín de los Andes; ArgentinaFil: Catalán, Mariano. Universidad Nacional del Comahue, Asentamiento Universitario San Martín de los Andes; ArgentinaFil: Laffitte, Lorena. Universidad Nacional del Comahue, Asentamiento Universitario San Martín de los Andes; ArgentinaFil: Andía, Ismael R. Universidad Nacional del Comahue, Asentamiento Universitario San Martín de los Andes; Argentin

Next-generation analysis of trypanosomatid genome stability and instability

No abstract available

Conditional genome engineering reveals canonical and divergent roles for the Hus1 component of the 9-1-1 complex in the maintenance of the plastic genome of Leishmania.

Leishmania species are protozoan parasites whose remarkably plastic genome limits the establishment of effective genetic manipulation and leishmaniasis treatment. The strategies used by Leishmania to maintain its genome while allowing variability are not fully understood. Here, we used DiCre-mediated conditional gene deletion to show that HUS1, a component of the 9-1-1 (RAD9- RAD1-HUS1) complex, is essential and is required for a G2/M checkpoint. By analyzing genome wide instability in HUS1 ablated cells, HUS1 is shown to have a conserved role, by which it preserves genome stability, and also a divergent role, by which it promotes genome variability. These roles of HUS1 are related to distinct patterns of formation and resolution of single-stranded DNA and γH2A, throughout the cell cycle. Our findings suggest that Leishmania 9-1-1 subunits have evolved to co-opt canonical genomic maintenance and genomic variation functions. Hence, this study reveals a pivotal function of HUS1 in balancing genome stability and transmission in Leishmania. These findings may be relevant to understanding the evolution of genome maintenance and plasticity in other pathogens and eukaryote

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy

Background: The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy.Patients and methods: A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays. Results: Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < −2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1–2.4] and with spine BMD (OR 1.4, 95% CI 1.1–1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < −2.5. Conclusion: Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures

The farnesoid X receptor regulates transcription of 3 beta-hydroxysteroid dehydrogenase type 2 in human adrenal cells

Recent studies have shown that the adrenal cortex expresses high levels of farnesoid X receptor (FXR), but its function remains not known. Herein, using microarray technology, we tried to identify candidate FXR targeting genes in the adrenal glands, and showed that FXR regulates 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in human adrenocortical cells. We further demonstrated that FXR stimulated HSD3B2 promoter activity and have defined the cis-element responsible for FXR regulation of HSD3B2 transcription. Transfection of H295R adrenocortical cells with FXR expression vector effectively increased FXR expression levels and additional treatment with chenodeoxycholic acid (CDCA) caused a 25-fold increase in the mRNA for organic solute transporter alpha (OSTα), a known FXR target gene. HSD3B2 mRNA levels also increased following CDCA treatment in a concentration-dependent manner. Cells transfected with a HSD3B2 promoter construct and FXR expression vector responded to CDCA with a 20-fold increase in reporter activity compared to control. Analysis of constructs containing sequential deletions of the HSD3B2 promoter suggested a putative regulatory element between -166 and -101. Mutation of an inverted repeat between -137 and -124 completely blocked CDCA/FXR induced reporter activity. Chromatin immunoprecipitation assays further confirmed the presence of a FXR response element in the HSD3B2 promoter. In view of the emerging role of FXR agonists as therapeutic treatment of diabetes and certain liver diseases, the effects of such agonists on other FXR expressing tissues should be considered. Our findings suggest that in human adrenal cells, FXR increases transcription and expression of HSD3B2. Alterations in this enzyme would influence the capacity of the adrenal gland to produce corticosteroids

Functional and genetic analysis in type 2 diabetes of Liver X receptor alleles – a cohort study

<p>Abstract</p> <p>Background</p> <p>Liver X receptor alpha <it>(LXRA</it>) and beta (<it>LXRB</it>) regulate glucose and lipid homeostasis in model systems but their importance in human physiology is poorly understood. This project aimed to determine whether common genetic variations in <it>LXRA </it>and <it>LXRB </it>associate with type 2 diabetes (T2D) and quantitative measures of glucose homeostasis, and, if so, reveal the underlying mechanisms.</p> <p>Methods</p> <p>Eight common single nucleotide polymorphisms in <it>LXRA </it>and <it>LXRB </it>were analyzed for association with T2D in one French cohort (N = 988 cases and 941 controls), and for association with quantitative measures reflecting glucose homeostasis in two non-diabetic population-based samples comprising N = 697 and N = 1344 adults. Investigated quantitative phenotypes included fasting plasma glucose, serum insulin, and HOMA_IRas measure of overall insulin resistance. An oral glucose tolerance test was performed in N = 1344 of adults. The two alleles of the proximal <it>LXRB </it>promoter, differing only at the SNP rs17373080, were cloned into reporter vectors and transiently transfected, whereupon allele-specific luciferase activity was measured. rs17373080 overlapped, according to <it>in silico </it>analysis, with a binding site for Nuclear factor 1 (NF1). Promoter alleles were tested for interaction with NF1 using direct DNA binding and transactivation assays.</p> <p>Results</p> <p>Genotypes at two <it>LXRB </it>promoter SNPs, rs35463555 and rs17373080, associated nominally with T2D (P values 0.047 and 0.026). No <it>LXRA </it>or <it>LXRB </it>SNP associated with quantitative measures reflecting glucose homeostasis. The rs17373080 C allele displayed higher basal transcription activity (P value < 0.05). The DNA-mobility shift assay indicated that oligonucleotides corresponding to either rs17373080 allele bound NF1 transcription factors in whole cell extracts to the same extent. Different NF1 family members showed different capacity to transactivate the <it>LXRB </it>gene promoter, but there was no difference between promoter alleles in NF1 induced transactivation activity.</p> <p>Conclusion</p> <p>Variations in the <it>LXRB </it>gene promoter may be part of the aetiology of T2D. However, the association between <it>LXRB </it>rs35463555 and rs17373080, and T2D are preliminary and needs to be investigated in additional larger cohorts. Common genetic variation in <it>LXRA </it>is unlikely to affect the risk of developing T2D or quantitative phenotypes related to glucose homeostasis.</p