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Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours
(2020-07) Haldbo-Classen, Lene; Amidi, Ali; Lukacova, Slavka; Wu, Lisa Maria; Oettingen, Gorm von; Lassen-Ramshad, Yasmin; Zachariae, Robert; Kallehauge, Jesper Folsted; Høyer, Morten; Department of Psychology
Background: Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions. Methods: A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤−1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model. Results: High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05). Conclusion: The present study indicates that the hippocampus may be vulnerable to radiation and that high radiation doses to the left hippocampus may lead to significant verbal learning and memory impairment. High RT doses to the left hippocampus and other left side structures may result in impairments in verbal fluency, executive function, and processing speed. Validation of these findings are being undertaken in a prospective study.
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SiGe nanocrystals in SiO2 with high photosensitivity from visible to short-wave infrared
(2020-02-24) Sultan, Muhammad Taha; Manolescu, Andrei; Department of Engineering
Films of SiGe nanocrystals (NCs) in oxide have the advantage of tuning the energy band gap by adjusting SiGe NCs composition and size. In this study, SiGe-SiO2 amorphous films were deposited by magnetron sputtering on Si substrate followed by rapid thermal annealing at 700, 800 and 1000 °C. We investigated films with Si:Ge:SiO2 compositions of 25:25:50 vol.% and 5:45:50 vol.%. TEM investigations reveal the major changes in films morphology (SiGe NCs with different sizes and densities) produced by Si:Ge ratio and annealing temperature. XPS also show that the film depth profile of SiGe content is dependent on the annealing temperature. These changes strongly influence electrical and photoconduction properties. Depending on annealing temperature and Si:Ge ratio, photocurrents can be 103 times higher than dark currents. The photocurrent cutoff wavelength obtained on samples with 25:25 vol% SiGe ratio decreases with annealing temperature increase from 1260 nm in SWIR for 700 °C annealed films to 1210 nm for those at 1000 °C. By increasing Ge content in SiGe (5:45 vol%) the cutoff wavelength significantly shifts to 1345 nm (800 °C annealing). By performing measurements at 100 K, the cutoff wavelength extends in SWIR to 1630 nm having high photoresponsivity of 9.35 AW−1.
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Enhancing neonatal immune responses with different vaccination strategies: Novel adjuvants and mucosal immunization.
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2026-10) Molina Estupiñan, Jenny Lorena; Stefanía P. Bjarnarson and Ingileif Jónsdóttir; Faculty of Medicine (UI); Læknadeild (HÍ); School of Health Sciences (UI); Heilbrigðisvísindasvið (HÍ)
Vaccination remains a cornerstone of global public health, significantly reducing mortality rates in infants and children. Despite substantial progress, infectious diseases continue to be a leading cause of death for children under five years of age, with 2.3 million fatalities occurring globally in the first month of life in 2022 alone. Many of these infections peak in incidence and severity during early infancy, before routine immunizations are initiated or can provide sufficient protection, highlighting the need for more effective preventive strategies in early life. Neonatal vaccination offers a promising approach by inducing immunity from birth and shortening this vulnerable period, supported by universal healthcare contact at delivery and thus high potential vaccination coverage, particularly in resource-limited settings. An ideal neonatal vaccine would offer a single-dose, needle-free immunization, eliciting immediate and long-lasting protection against multiple diseases. However, neonatal vaccination is challenged by the immaturity of the immune system, characterized by dampened innate responses, a Th2-biased T cell response profile, impaired germinal center (GC) formation, limited plasma cell survival and transient antibody (Ab) production, often resulting in suboptimal and short-lived immunity. Overcoming these limitations could be done with the development of safe and effective adjuvants and optimized immunization routes capable of inducing rapid and durable protective immune responses in early life. The overall aim of this thesis was to investigate how the route of immunization influences neonatal immune responses, with particular emphasis on intranasal (i.n.) versus subcutaneous (s.c.) vaccination, and how novel adjuvants modulate these responses to improve vaccine efficacy. Using a neonatal mouse model, we compared the effects of i.n. and s.c. administration with either mmCT or dmLT formulated with a pneumococcal conjugate vaccine, Pn1-CRM197, on serum Ab levels and Ab-secreting cells (ASCs) in the spleen and bone marrow (BM). Furthermore, we assessed the effects of immunization route, parenteral or mucosal administration, on the induction of B cell survival and activation receptors in the spleen, as well as plasma cell survival factors in the BM. Finally, we evaluated the dose-sparing capacity of the novel adjuvants mmCT, dmLT, CAF01 and CAF08b in comparison with the conventional adjuvant alum (aluminum hydroxide). Our focus was on primary neonatal Ab response, the persistence of ASCs and the protective capacity against two respiratory pathogens, Streptococcus pneumoniae and influenza virus. The results demonstrate that the route of immunization differentially shaped the kinetics of neonatal B cell activation and survival signaling. I.n. immunization induced earlier upregulation of BAFF-R, whereas s.c. immunization promoted earlier TACI expression and BAFF production which occurred at later time point following i.n. immunization, indicating distinct sequential programming of B cell survival and activation pathways. Despite these differences, i.n. and s.c. immunization with Pn1-CRM197 and mmCT or dmLT enhanced GC responses and persistence of vaccine-specific ASCs in BM. Notably, i.n. immunization accelerated plasmablast/plasma cell differentiation, increased BCMA expression, promoted earlier establishment of APRIL-rich BM plasma cell survival niches and enhanced the accumulation of vaccine-specific ASCs in the BM. Thus, these mechanistic changes translated into accelerated and sustained systemic and mucosal Ab responses, including persistent IgA production, while maintaining systemic IgG responses comparable to those induced by s.c. immunization. Together, these findings demonstrate that mucosal immunization accelerates neonatal B cell maturation and the establishment of long-lived humoral immunity by promoting the timely acquisition of key survival signals required for plasma cell differentiation and maintenance. In addition, the novel adjuvants mmCT, dmLT, CAF01 and CAF08b enabled substantial antigen dose sparing while maintaining protective immune responses against both pneumococcal and influenza antigens, although the magnitude of this effect depended on the vaccine. Collectively, this work demonstrates that rational selection of immunization routes and adjuvants can overcome key developmental limitations of neonatal immunity by promoting rapid B cell activation, durable plasma cell survival and long-lasting protective humoral immunity. In particular, i.n. immunization with Pn1-CRM197 and mmCT or dmLT enhanced systemic and mucosal humoral immune responses in the neonatal mouse model, highlighting the potential of mucosal vaccination with appropriate adjuvants as a promising strategy for accelerating protective immune responses early in life while simultaneously inducing systemic and mucosal immunity, providing important mechanistic and translational insights for the development of nextgeneration pediatric vaccines.
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Advice to patients undergoing stem cell transplant : Content analysis of survivor peer support narratives
(2018-05-01) Symes, Yael R.; Barrington, Clare; Austin, Jane; Wu, Lisa M.; Fisher, Edwin B.; Rini, Christine; Department of Psychology
Hematopoietic stem cell transplant survivors often share advice with patients undergoing this difficult treatment. We content analyzed narratives written by 59 transplant survivors given the opportunity to share advice with patients. Analyses described categories of advice they shared and evaluated their perceptions of the helpfulness of advice they had received. We found nine advice categories and evidence for variation in their perceived helpfulness, especially for advice to “be your own advocate,” “have someone you can rely on,” and “think positive.” Findings suggest the need to investigate how seemingly innocuous advice can be unhelpful and potentially distressing to some patients.
Verk
Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy
(2017-12-01) Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert; Department of Psychology
Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning. Methods: Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up. At follow-up, 22 participants had received cisplatin-based chemotherapy (CT) while 42 were in active surveillance (S). Brain structural networks were constructed for each participant, and network properties were investigated using graph theory and longitudinally compared across groups. Cognitive functioning was evaluated using standardized neuropsychological tests. All statistical tests were two-sided. Results: Compared with the S group, the CT group demonstrated altered global and local brain network properties from baseline to follow-up as evidenced by decreases in important brain network properties such as small-worldness (P =.04), network clustering (P =.04), and local efficiency (P =.02). In the CT group, poorer overall cognitive performance was associated with decreased small-worldness (r = -0.46, P =.04) and local efficiency (r = -0.51, P =.02), and verbal fluency was associated with decreased local efficiency (r = -0.55, P =.008). Conclusions: Brain structural networks may be disrupted following treatment with cisplatin-based chemotherapy. Impaired brain networks may underlie poorer performance over time on both specific and nonspecific cognitive functions in patients undergoing chemotherapy. To the best of our knowledge, this is the first study to longitudinally investigate changes in structural brain networks in a cancer population, providing novel insights regarding the neurobiological mechanisms of cancer-related cognitive impairment.

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