COPD and the Risk of Tuberculosis - A Population-Based Cohort Study

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. METHODS AND FINDINGS: All individuals > or = 40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). CONCLUSIONS: This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies

Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis.

IMPORTANCE: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. OBJECTIVE: To identify novel genetic loci and pathways associated with AS. DESIGN, SETTING, AND PARTICIPANTS: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019. EXPOSURES: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples. MAIN OUTCOMES AND MEASURES: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography. RESULTS: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]). CONCLUSIONS AND RELEVANCE: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target

The effects of plasticizers on the dynamic mechanical and thermal properties of poly(lactic acid)

Poly(lactic acid) (PLA) was blended with five plasticizers in a batchwise mixer and pressed into films. The films were analyzed by means of dynamic mechanical analysis and differential scanning calorimetry to investigate the properties of the blends. Triacetine and tributyl citrate proved to be effective as plasticizers when blended with PLA. The glass transition temperature of PLA decreased linearly as the plasticizer content was increased. Both plasticizers were miscible with PLA to an extent of similar to 25 wt %. At this point, the PLA seemed to be saturated with plasticizer and the blends tended to phase separate when more plasticizer was added. There were also signs of phase separation occurring in samples heated at 35, 50, and 80degreesC, most likely because of the material undergoing crystallization. The presence of the plasticizers induced an increased crystallinity by enhancing the molecular mobility

Preparation and properties of plasticized poly(lactic acid) films

Poly(lactic acid), PLA, was blended with monomeric and oligomeric plasticizers in order to enhance its flexibility and thereby overcome its inherent problem of brittleness. Differential scanning calorimetry, dynamic mechanical analysis, transmission electron microscopy, and tensile testing were used to investigate the properties of the blends. Monomeric plasticizers, such as tributyl citrate, TbC, and diethyl bishydroxymethyl malonate, DBM, drastically decreased the T-g of PLA, but the blends showed no morphological stability over time since rapid cold crystallization caused a size reduction of the amorphous domains in PLA. Consequently, the ability of PLA to accommodate the plasticizer diminished with the increase in crystallinity and migration of the plasticizer occurred. Increasing the molecular weight of the plasticizers by synthesizing oligoesters and oligoesteram ides resulted in blends that displayed T-g depressions slightly smaller than with the monomeric plasticizers. The compatibility with PLA was dependent on the molecular weight of the oligomers and on the presence or not of polar amide groups that were able to positively interact with the PLA chains. Aging the materials at ambient temperature revealed that the enhanced flexibility as well as the morphological stability of the films plasticized with the oligomers could be maintained as a result of the higher molecular weight and the polar interactions with PLA

Thermomechanical film properties and aging of blends of poly(lactic acid) and malonate oligomers

Malonate oligomers were synthesized as plasticizers for poly(lactic acid) (PLA). Esterification reactions were performed between diethyl bishydroxymethyl malonate (DBM) and either adipoyl dichloride or succinyl dichloride. Two molar masses were obtained within each series. Blending was carried out with PLA and the four oligomers as well as the monomeric unit from the syntheses (DBM). Dynamic mechanical analysis and differential scanning calorimetry were used to investigate the viscoelastic mechanical and thermal film properties of the blends. All the investigated plasticizers reduced the glass-transition temperature of PLA, and the plasticization effect was better for the plasticizers of low molar mass. However, the amorphous domains of PLA became saturated with plasticizer at a certain concentration, and phase separation occurred. A higher molar mass of the plasticizer caused this saturation to occur at lower plasticizer concentrations. Subsequently, the aging of the blends at the ambient temperature for 4 months induced phase separation in the blends containing DBM, whereas those with an oligomeric plasticizer were stable and remained compatible with PLA within the aging period. (C) 2004 Wiley Periodicals

Tributyl Citrate Oligomers as Plasticizers for Poly (lactic acid): Thermo-mechanical Film Properties and Aging

Poly (lactic acid), PLA, is a biodegradable thermoplastic that can be produced from renewable resources. The polymer is of interest for production of films for packaging applications. However, plasticization of PLA is required in order to obtain films with sufficient flexibility. PLA was blended with tributyl citrate (TbC) and two oligomers of TbC that were synthesized by transesterification of tributyl citrate (TbC) and diethylene glycol (DEG). Dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC) were used to investigate the dynamic mechanical and thermal properties of the blends. All the plasticizers investigated decreased the glass transition temperature of PLA, and the reduction was the largest with the plasticizer having the lowest molecular weight. The PLA matrix became saturated with plasticizer at a certain concentration and phase separation occurred; the higher the molecular weight of the plasticizer, the lower the saturation concentration. Aging of the blends at room temperature for several months induced partial phase separation in the material. It was observed that the morphological stability of the blends was enhanced when the plasticizer concentration was reasonably low, i.e. 10–15 wt%

Plasticization of poly(lactic acid) with oligomeric malonate esteramides: Dynamic mechanical and thermal film properties

Two oligomeric malonate esteramides and an oligomeric malonate ester were synthesized with the intention to plasticize poly(lactic acid), PLA. The synthesis was performed by reacting diethyl bishydroxymethyl malonate (DBM) with adipoyl dichloride and one of two diamines, that is, triethylene glycol diamine (TA) and polyoxypropylene glycol diamine (PA), or triethylene glycol (TEG), giving three platicizing agents denoted as DBMATA, DBMAPA, and DBMAT, respectively. The synthesis products were characterized by size exclusion chromatography and Fourier transform infrared spectroscopy, and blended with PLA at a concentration of 15 wt %. Dynamic mechanical analysis, differential scanning calorimetry, and tensile testing were used to investigate the physical properties of films from the resulting blends. All three plasticizers decreased the glass transition temperature of PLA, and the largest decrement was observed for PLA/DBMATA. Films of DBMATA and DBMAT showed enhanced flexibility in strain at break as compared to neat PLA. Subsequently, it was found that thermal annealing of the plasticized materials (4 h at 100 degrees C) encouraged cold crystallization, inducing phase separation in the blends, and caused them to regain the brittleness of neat PLA. On the other hand, by aging (6 weeks) the blends at ambient conditions, cold crystallization could be avoided and the flexibility in the films maintained. (c) 2005 Wiley Periodicals, Inc

Film Extrusion and Film Weldability of Poly(lactic acid) Plasticized with Triacetine and Tributyl Citrate.

Film extrusion and welding of biodegradable polymer films are important processes that must be considered in the development of compostable packaging materials. Film extrusion of poly(lactic acid) (PLA) has proved to be rather difficult because of its brittleness, but the flexibility of PLA can be improved by incorporation of a plasticizer in the material. PLA was plasticized with triacetine (TAc) and tributyl citrate (TbC). The blended materials and neat PLA were film extruded and the films were welded with constant heat (CH) welding. The films were analyzed by means of gas chromatography (GC), dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), contact angle measurements, and tensile testing. Storage of the plasticized films resulted in an increased crystallinity and changes in the film properties, rendering CH welding difficult. The welding process had no influence on thermal properties, such as cold crystallization temperature, melting temperature, crystallization temperature, and degree of crystallinity, of neat PLA but caused significant changes in the crystallinity of the plasticized materials. © 2003 Wiley Periodicals, Inc