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 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

Genetic variants determining survival and fertility in an adverse African environment:a population-based large-scale candidate gene association study

Molecular Technology and Informatics for Personalised Medicine and Healt

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

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

The Relation Between Histological, Tumor-Biological and Clinical Parameters in Deep and Superficial Leiomyosarcoma and Leiomyoma

Purpose: Leiomyosarcomas (LMS) of deep and superficial tissues were examined to identify prognostic markers explaining their different biological behaviour and to define differences between cutaneous and subcutaneous LMS. LMS and leiomyomas (LM) of the skin were compared to and consistent differences that could aid in the (sometimes difficult) diagnosis

Hydrosurgical and conventional debridement of burns:randomized clinical trial

Background: Tangential excision of burned tissue followed by skin grafting is the cornerstone of burn surgery. Hydrosurgery has become popular for tangential excision, with the hypothesis that enhanced preservation of vital dermal tissue reduces scarring. The aim of this trial was to compare scar quality after hydrosurgical versus conventional debridement before split-skin grafting. Methods: A double-blind randomized within-patient multicentre controlled trial was conducted in patients with burns that required split-skin grafting. One wound area was randomized to hydrosurgical debridement and the other to Weck knife debridement. The primary outcome was scar quality at 12 months, assessed with the observer part of the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes included complications, scar quality, colour, pliability, and histological dermal preservation. Results: Some 137 patients were randomized. At 12 months, scars of the hydrosurgical debrided wounds had a lower POSAS observer total item score (mean 2.42 (95 per cent c.i. 2.26 to 2.59) versus 2.54 (95 per cent c.i. 2.36 to 2.72; P =0.023)) and overall opinion score (mean 3.08 (95 per cent c.i. 2.88 to 3.28) versus 3.30 (95 per cent c.i. 3.09-3.51); P = 0.006). Patient-reported scar quality and pliability measurements were significantly better for the hydrosurgically debrided wounds. Complication rates did not differ between both treatments. Histologically, significantly more dermis was preserved with hydrosurgery (P < 0.001). Conclusion: One year after surgery scar quality and pliability was better for hydrosurgically debrided burns, probably owing to enhanced histological preservation of dermis

The Future of Biologic Agents in the Treatment of Sjögren’s Syndrome

The gain in knowledge regarding the cellular mechanisms of T and B lymphocyte activity in the pathogenesis of Sjögren’s syndrome (SS) and the current availability of various biological agents (anti-TNF-α, IFN- α, anti-CD20, and anti-CD22) have resulted in new strategies for therapeutic intervention. In SS, various phase I and II studies have been performed to evaluate these new strategies. Currently, B cell-directed therapies seem to be more promising than T cell-related therapies. However, large, randomized, placebo-controlled clinical trials are needed to confirm the promising results of these early studies. When performing these trials, special attention has to be paid to prevent the occasional occurrence of the severe side effects

Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation

Background: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals. Methods: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established. Results: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher’s exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1–4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5′ end of the gene. Conclusions: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD