Polyphenols-Ensured Accessibility from Food to the Human Metabolism by Chemical and Biotechnological Treatments.

Polyphenols are plant-based compounds famous for their positive impact on both human health and the quality of food products. The benefits of polyphenols are related to reducing cardiovascular diseases, cholesterol management, cancers, and neurological disorders in humans and increasing the shelf life, management of oxidation, and anti-microbial activity in food products. The bioavailability and bio-accessibility of polyphenols are of the highest importance to secure their impact on human and food health. This paper summarizes the current state-of-the-art approaches on how polyphenols can be made more accessible in food products to contribute to human health. For example, by using food processing methods including various technologies, such as chemical and biotechnological treatments. Food matrix design and simulation procedures, in combination with encapsulation of fractionated polyphenols utilizing enzymatic and fermentation methodology, may be the future technologies to tailor specific food products with the ability to ensure polyphenol release and availability in the most suitable parts of the human body (bowl, intestine, etc.). The development of such new procedures for utilizing polyphenols, combining novel methodologies with traditional food processing technologies, has the potential to contribute enormous benefits to the food industry and health sector, not only reducing food waste and food-borne illnesses but also to sustain human health.

Surgeon volume and patient-reported urinary incontinence after radical prostatectomy. Population-based register study in Sweden.

OBJECTIVE: To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. METHODS: A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: 'How much urine leakage do you experience?' with the response alternatives 'Not at all', 'A little', defined as continence and 'Moderately', 'Much/Very much' as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. RESULTS: 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48-3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04-1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26-1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. CONCLUSIONS: The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results.

Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer.

Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design setting and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer.

Satisfaction with Nurse-led Follow-up in Prostate Cancer Patients-A Nationwide Population-based Study.

Background: Satisfaction with nurse-led follow-up among men with prostate cancer is high. However, it is unclear whether all men are satisfied or whether there are men who would benefit from being followed by a urologist or a nurse. Objective: To investigate the follow-up distribution between urologists and nurses, and whether the high self-reported satisfaction with nurse-led follow-up is independent of other factors such as age or comorbidity.Design, setting, and participants:All Swedish men, ≤70 yr of age, with a low-risk prostate cancer diagnosis in 2008, answered a questionnaire 7 yr after diagnosis. The extensive questionnaire included a question on satisfaction with care, answered on a seven-point scale. Participants were divided based on whether they were followed up by a nurse, a urologist, or both.Outcome measurements and statistical analysis:Factors that could influence the level of satisfaction were identified as age, education, comorbidity, treatment, disease progression, urinary bother, level of information, and participation in treatment decision. Likelihood ratio tests from ordinal regression were used to test the null hypothesis of similar satisfaction between groups. Results and limitations: Out of 1288 men, 1137 (88%) answered both the question on who performed the follow-up and the question regarding satisfaction. In all, 350 men reported that they were followed up by nurses (31%), 598 (52%) by urologists, and 189 (17%) by both. No differences in satisfaction where seen between the groups. Approximately 50% were satisfied completely, regardless of who performed the follow-up. Results were not affected by age, educational level, comorbidity, treatment, disease progression, urinary bother, information, or participation in treatment decision. Limitations include the nonrandomized, retrospective design and a potential recall bias. Conclusions: Satisfaction with nurse-led follow-up is high, regardless of factors such as age, level of education, comorbidity, and treatment. Patient summary: Men with prostate cancer can be offered nurse-led follow-up on a regular basis and still maintain their satisfaction with health care.

Clustering and cross-linking of the wheat storage protein α-gliadin: A combined experimental and theoretical approach.

Our aim was to understand mechanisms for clustering and cross-linking of gliadins, a wheat seed storage protein type, monomeric in native state, but incorporated in network while processed. The mechanisms were studied utilizing spectroscopy and high-performance liquid chromatography on a gliadin-rich fraction, in vitro produced α-gliadins, and synthetic gliadin peptides, and by coarse-grained modelling, Monte Carlo simulations and prediction algorithms. In solution, gliadins with α-helix structures (dip at 205 nm in CD) were primarily present as monomeric molecules and clusters of gliadins (peaks at 650- and 700-s on SE-HPLC). At drying, large polymers (Rg 90.3 nm by DLS) were formed and ß-sheets increased (14% by FTIR). Trained algorithms predicted aggregation areas at amino acids 115-140, 150-179, and 250-268, and induction of liquid-liquid phase separation at P- and Poly-Q-sequences (Score = 1). Simulations showed that gliadins formed polymers by tail-to-tail or a hydrophobic core (Kratky plots and Ree = 35 and 60 for C- and N-terminal). Thus, the N-terminal formed clusters while the C-terminal formed aggregates by disulphide and lanthionine bonds, with favoured hydrophobic clustering of similar/exact peptide sections (synthetic peptide mixtures on SE-HPLC). Mechanisms of clustering and cross-linking of the gliadins presented here, contribute ability to tailor processing results, using these proteins.

Site-specific functional roles of the Factor X activation peptide in the intrinsic tenase-mediated Factor X activation.

The conversion of zymogen Factor X (FX) to an active protease involves the removal of a 52-residue long activation peptide (AP). Through site-directed mutagenesis, we investigate the role of the AP and demonstrate that the high abundance of proline residues is important for efficient proteolysis of FX. Moreover, we identify an essential interaction site for Factor IXa (FIXa) between residues 22 and 30 (AP numbering) and find that the residues between 31 and 41 may provide an important interaction site for the intrinsic tenase complex, composed of Factor IXa (FIXa) and Factor VIIIa (FVIIIa). Finally, we suggest that the carbohydrate chain at Asn-39 restricts the activator specificity, as elimination of this glycosylation site increases the activation rate for activation by FIXa and FXa.

Development of Cagrilintide, a Long-Acting Amylin Analogue.

A hallmark of the pancreatic hormone amylin is its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug design effort. The amylin analogue pramlintide is commercially available for diabetes treatment as an adjunct to insulin therapy but requires three daily injections due to its short half-life. We report here the development of the stable, lipidated long-acting amylin analogue cagrilintide (23) and some of the structure-activity efforts that led to the selection of this analogue for clinical development with obesity as an indication. Cagrilintide is currently in clinical trial and has induced significant weight loss when dosed alone or in combination with the GLP-1 analogue semaglutide.

Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study.

BACKGROUND AND OBJECTIVE: Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group. METHODS: 9,810 RARP's registered in the National Prostate Cancer Register of Sweden (2015-2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection. RESULTS: Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11-11.91), hospital (OR 2.16, 95% CI 1.53-3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07-3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34-3.57), hospital (OR 2.02, 95% CI 1.66-2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54-2.35), hospital (OR 1.28, 95% CI 1.07-1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment. CONCLUSIONS: High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.

PSA testing patterns in a large Swedish cohort before the implementation of organized PSA testing.

BACKGROUND: Organized PSA testing for asymptomatic men aged 50-74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs. METHOD: We included all men in the Uppsala-Örebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala-Örebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala-Örebro region during this time period. RESULTS: Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level ≤1µg/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively. CONCLUSION: Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.

Changes in lifestyle among prostate cancer survivors: A nationwide population-based study.

OBJECTIVE: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life. METHODS: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change. RESULTS: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life. CONCLUSIONS: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.

Glutenin and Gliadin, a Piece in the Puzzle of their Structural Properties in the Cell Described through Monte Carlo Simulations.

Gluten protein crosslinking is a predetermined process where specific intra- and intermolecular disulfide bonds differ depending on the protein and cysteine motif. In this article, all-atom Monte Carlo simulations were used to understand the formation of disulfide bonds in gliadins and low molecular weight glutenin subunits (LMW-GS). The two intrinsically disordered proteins appeared to contain mostly turns and loops and showed "self-avoiding walk" behavior in water. Cysteine residues involved in intramolecular disulfide bonds were located next to hydrophobic peptide sections in the primary sequence. Hydrophobicity of neighboring peptide sections, synthesis chronology, and amino acid chain flexibility were identified as important factors in securing the specificity of intramolecular disulfide bonds formed directly after synthesis. The two LMW-GS cysteine residues that form intermolecular disulfide bonds were positioned next to peptide sections of lower hydrophobicity, and these cysteine residues are more exposed to the cytosolic conditions, which influence the crosslinking behavior. In addition, coarse-grained Monte Carlo simulations revealed that the protein folding is independent of ionic strength. The potential molecular behavior associated with disulfide bonds, as reported here, increases the biological understanding of seed storage protein function and provides opportunities to tailor their functional properties for different applications.

Development and validation of a prediction model for identifying men with intermediate- or high-risk prostate cancer for whom bone imaging is unnecessary: a nation-wide population-based study.

Objective: To develop and validate a nomogram that identifies men for whom bone scan is unnecessary.Material and methods: The study datasets were derived from the National Prostate Cancer Register (NPCR) of Sweden. All men in the NPCR ≤80 years of age who were diagnosed with intermediate- or high-risk prostate cancer and who had pretreatment bone imaging (99mTc MDP scintigraphy, plain x-ray, computed tomography, magnetic resonance imaging, and/or positron emission tomography fused with computed tomography) were included. Men diagnosed from 2015-2016 formed a development dataset and men diagnosed in 2017 formed a validation dataset. Outcome was metastasis on bone imaging as registered in NPCR. Multivariable logistic regression was used to develop a nomogram.Results: In the development dataset 482/5084 men (10%) had bone metastasis, the corresponding percentage in the validation dataset was 282/2554 (11%). Gleason grade group, clinical T stage, and prostate-specific antigen were included in the final model. Discrimination and calibration were satisfactory in both the development (AUC 0.80, 95% CI 0.78-0.82) and validation dataset (AUC 0.80, 95% CI, 0.77-0.82). Compared with using the EAU guidelines' recommendation for selecting men for imaging, using the nomogram with a cut-off at 4% chance of bone metastasis, would have avoided imaging in 519/2068 men (25%) and miss bone metastasis in 10/519 (2%) men in the validation dataset.Conclusion: By use of our nomogram, bone scans of men with prostate cancer can be avoided in a large proportion of men.

Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study.

OBJECTIVE: Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance. DESIGN, SETTING AND PARTICIPANTS: In 2015, we sent a questionnaire to all Swedish men aged ≤70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS. RESULTS: 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7 years. Most men (83%) choose AS because 'My doctor recommended AS'. Factors associated with choosing AS over treatment were older age (OR 1.81, 95% CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95% CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95% CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95% CI 0.10 to 0.63). The reason for having treatment after initial AS was 'the PSA level was rising' in 55% and biopsy findings in 36%. CONCLUSIONS: A doctor's recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.

PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design.

INTRODUCTION: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. METHODS AND ANALYSIS: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. ETHICS AND DISSEMINATION: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02914873.

Population-based, nationwide registration of prostatectomies in Sweden.

INTRODUCTION: Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. METHODS: In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. RESULTS: Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). CONCLUSIONS: We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.

The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS).

BACKGROUND: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown. OBJECTIVE: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance. DESIGN, SETTING, AND PARTICIPANTS: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included. INTERVENTION: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measure: Gleason grade group ≥2 cancer. SECONDARY OUTCOMES: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied. RESULTS AND LIMITATIONS: Gleason grade group ≥2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p=0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p=0.004) and for Gleason grade group ≥2 cancer 2.3 (95% CI 1.2-4.4, p=0.015) per 0.1-ng/ml/cm3 increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used. CONCLUSIONS: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy. PATIENT SUMMARY: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy.

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer.

BACKGROUND: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias. OBJECTIVE: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study. DESIGN, SETTING, AND PARTICIPANTS: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n=2078) or GnRH agonists (n=4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5yr before through to 5yr after starting androgen deprivation therapy (ADT). OUTCOME MEASURES AND STATISTICAL METHODS: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses. RESULTS AND LIMITATIONS: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p<0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-1.44). CONCLUSIONS: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment. PATIENT SUMMARY: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

Unraveling the Structural Puzzle of the Giant Glutenin Polymer-An Interplay between Protein Polymerization, Nanomorphology, and Functional Properties in Bioplastic Films.

A combination of genotype, cultivation environment, and protein separation procedure was used to modify the nanoscale morphology, polymerization, and chemical structure of glutenin proteins from wheat. A low-polymerized glutenin starting material was the key to protein-protein interactions mainly via SS cross-links during film formation, resulting in extended ß-sheet structures and propensity toward the formation of nanoscale morphologies at molecular level. The properties of glutenin bioplastic films were enhanced by the selection of a genotype with a high number of cysteine residues in its chemical structure and cultivation environment with a short grain maturation period, both contributing positively to gluten strength. Thus, a combination of factors affected the structure of glutenins in bioplastic films by forming crystalline ß-sheets and propensity toward the ordered nanostructures, thereby resulting in functional properties with high strength, stiffness, and extensibility.

Occupational status among adult survivors following allogeneic stem cell transplantation in childhood.

This study examined occupational status and factors associated with sick leave and disability pension among adult long-term survivors previously treated with allogeneic stem cell transplantation (allo-SCT) during childhood. Moreover, occupational status was compared to that of a reference group. Data were collected with questionnaires and from medical records. The SCT group included 59 adults (18-45 years old: response rate 63%) treated with allo-SCT in childhood with a median of 17 (range 3-28) years earlier. The reference group included 296 individuals randomly selected from the general population. The results show that 54% of the long-term survivors were working part- or full-time and that 19% were on sick leave or disability pension. A larger proportion of the SCT group was on sick leave or disability pension (19% vs. 6%: p < .001) than of the reference group. The logistic regression analysis revealed that being on sick leave or disability pension among long-term survivors was associated with late effects related to the allo-SCT (OR 12.28: 95% CI 1.3-111.6: p = .03). The results underscore that long-term survivors' engagement in paid work is influenced many years after treatment and highlights the need to include vocational assistance in the rehabilitation following allo-SCT in childhood.