Physical activity, body mass index and prostate cancer : studies of risk, progression and mortality

Prostate cancer is the most common cancer among men in developed countries, but it is still unclear what causes the disease. Body mass index (BMI) and physical activity are modifiable lifestyle factors with the potential to influence the development and progression of prostate tumors and may provide alternative strategies for reducing both prostate cancer incidence and mortality. This thesis includes studies of the importance of body weight and physical activity on prostate cancer as well as methodological studies of how to assess physical activity in epidemiological studies. In Study I and II we aim to clarify the effect of BMI, weight change and physical activity on prostate cancer progression and mortality, while we in Study V aim to investigate the associations between BMI, serum prostate specific antigen (PSA) and the risk of prostate cancer. In Study III and IV we aim to assess the validity of the new web-based physical activity questionnaire Active-Q against three different reference methods. In Study I and II, we found that high BMI was associated with increased rates of overall mortality, but not progression or prostate cancer specific mortality, in men diagnosed with localized prostate cancer. An increase in body weight by >5% after diagnosis was associated with a higher prostate cancer specific mortality, while a weight reduction by >5% after diagnosis was associated with higher overall mortality. Frequent walking/bicycling and exercise were associated with lower prostate cancer specific and overall mortality, compared to a less active lifestyle. Moreover, high levels of total recreational activity and household work were associated with lower overall mortality. Study V showed that men with high BMI had lower serum PSA-levels, compared to men with normal BMI. Although BMI was not associated with overall prostate cancer risk, there was a suggested association between high BMI and high-grade prostate cancer. Active-Q was validated with regards to energy expenditure and total MET-hours against doubly labelled water and pedometers in Study III and with regards to time spent in different intensity levels of activity against accelerometers in Study IV. Active-Q showed moderate validity compared to the reference methods and good absolute agreement for energy expenditure while a somewhat lower agreement for time at different intensity levels was seen. When comparing repeated Active-Q assessments, the questionnaire showed high reproducibility. In conclusion, a physically active lifestyle after prostate cancer diagnosis is beneficial and associated with lower levels of both overall and prostate cancer specific mortality. Our results also showed that a large increase in body weight after diagnosis was associated with higher prostate cancer specific mortality, whereas weight reduction was associated increased higher overall mortality. Although we did not find a clear effect of BMI on overall prostate cancer risk, progression or prostate cancer specific mortality, we found that men with high BMI had lower levels of serum PSA, potentially hampering early detection of prostate cancer. Weight maintenance and a physically active lifestyle after diagnosis may complement prostate cancer treatment to improve survival. Also, Active-Q is a valid method for assessing energy expenditure and time spent at different intensity levels in future epidemiological studies

Hauerwas and the Law: Framing a Productive Conversation

Background: Meal-Q and its shorter version, MiniMeal-Q, are 2 new Web-based food frequency questionnaires. Their meal-based and interactive format was designed to promote ease of use and to minimize answering time, desirable improvements in large epidemiological studies. Objective: We evaluated the validity of energy and macronutrient intake assessed with Meal-Q and MiniMeal-Q as well as the reproducibility of Meal-Q. Methods: Healthy volunteers aged 20-63 years recruited from Stockholm County filled out the 174-item Meal-Q. The questionnaire was compared to 7-day weighed food records (WFR; n=163), for energy and macronutrient intake, and to doubly labeled water (DLW; n=39), for total energy expenditure. In addition, the 126-item MiniMeal-Q was evaluated in a simulated validation using truncated Meal-Q data. We also assessed the answering time and ease of use of both questionnaires. Results: Bland-Altman plots showed a varying bias within the intake range for all validity comparisons. Cross-classification of quartiles placed 70%-86% in the same/adjacent quartile with WFR and 77% with DLW. Deattenuated and energy-adjusted Pearson correlation coefficients with the WFR ranged from r=0.33-0.74 for macronutrients and was r=0.18 for energy. Correlations with DLW were r=0.42 for Meal-Q and r=0.38 for MiniMeal-Q. Intraclass correlations for Meal-Q ranged from r=0.57-0.90. Median answering time was 17 minutes for Meal-Q and 7 minutes for MiniMeal-Q, and participants rated both questionnaires as easy to use. Conclusions: Meal-Q and MiniMeal-Q are easy to use and have short answering times. The ranking agreement is good for most of the nutrients for both questionnaires and Meal-Q shows fair reproducibility.QC 20130709</p

Women's Reasons to Seek Bariatric Surgery and Their Expectations on the Surgery Outcome - a Multicenter Study from Five European Countries

Purpose Understanding patients' reasons for having bariatric surgery and their expectation on surgery outcomes is important to provide the best clinical practice and reduce unrealistic expectations. It is unknown if reasons and expectations differ between countries. We aimed to investigate the reasons for seeking bariatric surgery and expectations of surgical outcomes among patients in five European countries. Methods In total, 250 women accepted for bariatric surgery were recruited: 50 women each from Finland, Germany, Norway, Sweden, and the Netherlands. Participants ranked 14 reasons for seeking surgery, and reported the three primary reasons. They also reported expectations on weight loss and impact of surgery vs. lifestyle on weight loss outcomes. Results Mean age and body mass index were 42.9 +/- 11.5 years and 45.1 +/- 6.2 kg/m(2), respectively. Weight loss and improved co-morbidity were ranked as the most important reasons. Participants expected to lose between 70.8 and 94.3% of their excessive weight. The expected impact of surgery as a driver of weight loss was higher in Germany and the Netherlands compared to in Finland, Norway, and Sweden where participants expected lifestyle changes to also have an impact. Conclusion Weight loss and improved co-morbidities were the main reasons for undergoing bariatric surgery. Expectations on weight loss were generally very high, but expectations of surgery vs. lifestyle as the main driver of weight loss differed between countries. While some patients understand the importance of lifestyle change and maintenance of a healthy lifestyle after surgery in order to obtain a successful weight loss, other may need additional counselling.Peer reviewe

Imaging the real space structure of the spin fluctuations in an iron-based superconductor

Spin fluctuations are a leading candidate for the pairing mechanism in high temperature superconductors, supported by the common appearance of a distinct resonance in the spin susceptibility across the cuprates, iron-based superconductors and many heavy fermion materials1. The information we have about the spin resonance comes almost exclusively from neutron scattering. Here we demonstrate that by using low-temperature scanning tunneling microscopy and spectroscopy we can characterize the spin resonance in real space. We establish that inelastic tunneling leads to the characteristic "dip-hump" feature seen in tunneling spectra in high temperature superconductors and that this feature arises from excitations of the spin fluctuations. Spatial mapping of this feature near defects allows us to probe non-local properties of the spin susceptibility and to image its real space structure.Publisher PDFPeer reviewe

Bacterial symbiont subpopulations have different roles in a deep-sea symbiosis

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hinzke, T., Kleiner, M., Meister, M., Schlueter, R., Hentschker, C., Pane-Farre, J., Hildebrandt, P., Felbeck, H., Sievert, S. M., Bonn, F., Voelker, U., Becher, D., Schweder, T., & Markert, S. Bacterial symbiont subpopulations have different roles in a deep-sea symbiosis. Elife, 10, (2021): e58371, https://doi.org/10.7554/eLife.58371.The hydrothermal vent tubeworm Riftia pachyptila hosts a single 16S rRNA phylotype of intracellular sulfur-oxidizing symbionts, which vary considerably in cell morphology and exhibit a remarkable degree of physiological diversity and redundancy, even in the same host. To elucidate whether multiple metabolic routes are employed in the same cells or rather in distinct symbiont subpopulations, we enriched symbionts according to cell size by density gradient centrifugation. Metaproteomic analysis, microscopy, and flow cytometry strongly suggest that Riftia symbiont cells of different sizes represent metabolically dissimilar stages of a physiological differentiation process: While small symbionts actively divide and may establish cellular symbiont-host interaction, large symbionts apparently do not divide, but still replicate DNA, leading to DNA endoreduplication. Moreover, in large symbionts, carbon fixation and biomass production seem to be metabolic priorities. We propose that this division of labor between smaller and larger symbionts benefits the productivity of the symbiosis as a whole.This work was supported by the German Research Foundation DFG (grant MA 6346/2–1 to SM), fellowships of the Institute of Marine Biotechnology Greifswald (TH, MM), a German Academic Exchange Service (DAAD) grant (TH), the NC State Chancellor’s Faculty Excellence Program Cluster on Microbiomes and Complex Microbial Communities (MK), the USDA National Institute of Food and Agriculture, Hatch project 1014212 (MK), the U.S. National Science Foundation (grants OCE-1131095 and OCE-1559198 to SMS), and The WHOI Investment in Science Fund (to SMS). We furthermore acknowledge support for article processing charges from the DFG (Grant 393148499) and the Open Access Publication Fund of the University of Greifswald

Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage

BACKGROUND: The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells. RESULTS: By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability. CONCLUSIONS: Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01167-1

Background risk of breast cancer and the association between physical activity and mammographic density

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A Digital Platform and Smartphone App to Increase Physical Activity in Patients With Type 2 Diabetes: Overview Of a Technical Solution

Mobile Health (mHealth) solutions can be used to increase patients engagement in self-care. Descriptions of the technical solutions behind mHealth smartphone apps may guide the development of future apps. Here, we aim to describe the technical background and visual display of the DiaCert system, which was developed to support daily walking among patients with type 2 diabetes. The DiaCert system publishes one application program interface developed for patient devices (ie, smartphone apps running on iOS or Android) and another for web-based health care provider components (ie, administrative components). An individual care plan is created for each patient on the caregiver platform, and data on physical activity (ie, steps), blood samples, and questionnaires are shared between patient and caregiver in the DiaCert system. Technical solutions such as this enable us to reach more individuals at a lower cost compared to traditional health care. An advantage to the DiaCert technical solution is that it is built on a simple architecture and therefore is easily scalable. However, as it is a separate solution, it means adding yet another process for health care personnel to integrate into their work, which must be acknowledged. We hope that the technical description and visual display of the DiaCert system herein can guide researchers in the design and building of new and effective mHealth solutions.Funding Agencies|Stockholm County Council; Karolinska Institutet; Swedish Research Council for Health, Working Life, and Welfare; Swedish government; county councils [2016-00985]; Strategic Research Area in Care Sciences; [20170784]</p