Modifiers of breast cancer risk in BRCA1/2 mutation carriers: diagnostic radiation, physical activity, and body weight

Leeuwen, F.E. van [Promotor]Rookus, M.A. [Copromotor

Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women

Objective¿ Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake. Methods and Results¿ Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: -0.51 m/s (95% CI -1.00 to -0.03, fourth versus first quartile, P for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: -0.42 m/s (95% CI -0.93 to 0.11, fourth versus first quartile, P for trend=0.06). Results were most pronounced in older women: for isoflavones, -0.94 m/s (95% CI -1.65 to -0.22, P for trend=0.02), and for lignans, -0.80 m/s (95% CI -1.85 to -0.05), fourth versus first quartile. Conclusions¿ The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older wome

The evolution of lifespan in the butterfly Bicyclus anynana

The general aim of the work described in this thesis is to help explain the variation in ageing by using the life history framework of B. anynana. Each chapter focuses on a different aspect of the life history, together giving a complete picture of the origins of variation in ageing in this species. A central theme to every chapter is the relative influence of genes, the environment, and how they related to plasticity. A summarising discussion of all chapters, and a perspective on how the ideas in this thesis will contribute to ageing research in the future is also included.LEI Universiteit LeidenDutch Ministry of Economic Affairs, Unilever Corporate Research in Colworth, United Kingdom, Numico Research BV in Wageningen the NetherlandsEvolutiebiologi

Early implant placement with or without alveolar ridge preservation in single tooth gaps renders similar esthetic, clinical and patient-reported outcome measures: One-year results of a randomized clinical trial

OBJECTIVES To test whether early implant placement with alveolar ridge preservation (ARP) results in different esthetic, clinical and patient-reported outcome measures (PROMs) compared with early implant placement without ARP. MATERIAL AND METHODS Seventy-five patients requiring single tooth extraction in the anterior maxilla were recruited. Following tooth extraction, the patients were randomly allocated to three groups: (a) ARP using demineralized bovine bone mineral containing 10% collagen (DBBM-C) covered by a collagen matrix (CM) (n = 25), (b) ARP using DBBM-C covered with a palatal graft (PG) (n = 25) and (c) spontaneous healing (control) (n = 25). Eight weeks after tooth extraction, a CBCT was taken and early implant placement was performed in all patients. Esthetic, clinical and PROMs were evaluated one year post-loading. RESULTS A total of 70 patients were available for re-examination at one year post-loading. The median mid-facial mucosal margin change amounted to -0.02 mm (IQR -0.27-0.46) in the CM group, -0.13 mm (IQR -0.44-0.25) in the PG group and -0.14 mm (IQR -0.29-0.07) in the control group, with no significant differences between the groups. Mean PES scores amounted to 7.0 ± 1.4 in the CM group, 7.1 ± 1.5 in the PG group and 7.3 ± 1.7 in the control group without significant differences between the groups. Plaque, bleeding on probing and probing depth did not differ between treatment groups. PROMs in general revealed no significant differences between the groups. CONCLUSION Early implant placement with ARP using either a collagen matrix or a palatal graft rendered similar esthetic, clinical and PROMs to early implant placement without ARP. When a failing tooth can be replaced with an implant within 2 months after tooth extraction, the added value of ARP might be clinically negligible

A sensitive method to extract DNA from biological traces present on ammunition for the purpose of genetic profiling

Exploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is nowadays more and more the rule rather than the exception. On many crime scenes, cartridges, bullets, and casings (jointly abbreviated as CBCs) are regularly found, and even after firing, these potentially carry trace amounts of biological material. Since 2003, the Forensic Laboratory for DNA Research is routinely involved in the forensic investigation of CBCs in the Netherlands. Reliable DNA profiles were frequently obtained from CBCs and used to match suspects, victims, or other crime scene-related DNA traces. In this paper, we describe the sensitive method developed by us to extract DNA from CBCs. Using PCR-based genotyping of autosomal short tandem repeats, we were able to obtain reliable and reproducible DNA profiles in 163 out of 616 criminal cases (26.5%) and in 283 out of 4,085 individual CBC items (6.9%) during the period January 2003–December 2009. We discuss practical aspects of the method and the sometimes unexpected effects of using cell lysis buffer on the subsequent investigation of striation patterns on CBCs

Stromal vascular fraction-enriched fat grafting as treatment of adherent scars:study design of a non-randomized early phase trial

BACKGROUND: In the last decades, autologous fat grafting has been used to treat adherent dermal scars. The observed regenerative and scar-reducing properties have been mainly ascribed to the tissue-derived stromal vascular fraction (tSVF) in adipose tissue. Adipose tissue's components augment local angiogenesis and mitosis in resident tissue cells. Moreover, it promotes collagen remodeling. We hypothesize that tSVF potentiates fat grafting-based treatment of adherent scars. Therefore, this study aims to investigate the effect of tSVF-enriched fat grafting on scar pliability over a 12-month period.METHODS AND DESIGN: A clinical multicenter non-randomized early phase trial will be conducted in two dedicated Dutch Burn Centers (Red Cross Hospital, Beverwijk, and Martini Hospital, Groningen). After informed consent, 46 patients (≥18 years) with adherent scars caused by burns, necrotic fasciitis, or degloving injury who have an indication for fat grafting will receive a sub-cicatricic tSVF-enriched fat graft. The primary outcome is the change in scar pliability measured by the Cutometer between pre- and 12 months post-grafting. Secondary outcomes are scar pliability (after 3 months), scar erythema, and melanin measured by the DSM II Colormeter; scar quality assessed by the patient and observer scales of the Patient and Observer Scar Assessment Scale (POSAS) 2.0; and histological analysis of scar biopsies (voluntary) and tSVF quality and composition. This study has been approved by the Dutch Central Committee for Clinical Research (CCMO), NL72094.000.20.CONCLUSION: This study will test the clinical efficacy of tSVF-enriched fat grafting to treat dermal scars while the underlying working mechanism will be probed into too.TRIAL REGISTRATION: Dutch Trial Register NL 8461. Registered on 16 March 2020.</p

The Role of Burn Centers in the Treatment of Necrotizing Soft-Tissue Infections:A Nationwide Dutch Study

Patients with extensive and complex wounds due to Necrotizing Soft-Tissue Infections (NSTI) may be referred to a burn center. This study describes the characteristics, outcomes, as well as diagnostic challenges of these patients. Patients admitted to three hospitals with a burn center for the treatment of NSTI in a 5-year period were included. Eighty patients (median age 54 years, 60% male) were identified, of whom 30 (38%) were referred by other centers, usually after survival of the initial septic phase. Those referred from other centers, compared to those primarily admitted to the study hospitals, were more likely to have group A streptococcal involvement (62% vs 35%, p = .02), larger wounds (median 7% vs 2% total body surface area, p &lt; .001), and a longer length of stay (median 49 vs 22 days, p &lt; .001). Despite a high incidence of septic shock (50%), the mortality rate was low (12%) for those primarily admitted. Approximately half (53%) of the patients were initially misdiagnosed upon presentation, which was associated with delay to first surgery (16 hours vs 4 hours, p &lt; .001). Those initially misdiagnosed had more (severe) comorbidities, and less frequently reported pain or blue livid discoloration of the skin. This study underlines the burn centers' function as referral centers for extensively affected patients with NSTI. Besides the unique wound and reconstructive expertise, the low mortality rate indicates these centers provide adequate acute care as well. A major remaining challenge remains recognition of the disease upon presentation. Future studies in which factors associated with misdiagnosis are explored are needed.</p

Accumulation of Self-Reactive Naive and Memory B Cell Reveals Sequential Defects in B Cell Tolerance Checkpoints in Sjogren's Syndrome

This work was funded by grants number 18237 and 20089 from Arthritis Research UK (http://www.arthritisresearchuk.org) to MB and the William Harvey Research Foundation. EC was recipient of short-term travel fellowships from EMBO (ASTF 318-2010) and EFIS-IL

A 57-year-old man who developed arthritis during R-CHOP chemotherapy for non-Hodgkin lymphoma

Rituximab is a chimeric human-mouse anti-CD20 monoclonal antibody, which is used in the treatment of both B-cell lymphomas and rheumatic diseases. We describe a case of a previously healthy 57-year-old man developing arthritis while being treated with rituximab-CHOP chemotherapy (R-CHOP) for a non-Hodgkin lymphoma. The remittant arthritis developed at successively shorter time-intervals after R-CHOP administration and only improved after rituximab was removed from the chemotherapy schedule, suggesting a rituximab-related phenomenon, as extensive diagnostic testing ruled out any other diagnosis